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Early Allograft Dysfunction and Biliary Strictures After Liver Transplantation

Mustafa Arain, MDAssociate Professor of MedicineDirector of Advanced EndoscopyUniversity of California – San Francisco

mustafa.arain@ucsf.edu

Disclosures

Consultant for Boston Scientific and Olympus

No off-label use of devices and equipment

Outline

Indications and anatomic considerations

Diagnostic evaluation

Endoscopic interventions

Living donor liver transplant (LDLT)

Indications- Biliary Complications

Strictures

Leaks

Stones

Early - Days

Early – OccasionallyLate – Weeks to Years

Late – Months to Years

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ERCP for elevated LFTs and suspected anastomotic stricture

? StrictureAir in the biliary tree

Patient with a Roux-en-Y Hepatico-jejunosotomy

Anatomic Considerations

Ductal anatomy

Type of surgery – type of liver donation

Understanding of segmental and sectoral anatomy

Ductal Anatomy

Choledocho- dochalanastomosis

- Aka duct to duct (DD) anastomosis

- Most common

- Easy endoscopic access

- Availability of a wide selection of accessories and stents

Donor duct

Recipient duct

Anastomosis(with stricture)

Ductal Anatomy

Roux-en-Y hepatico-jejunostomy

- Enteroscopy assisted ERCP

- Need to reach jejuno-jejunal anastomosis and then advance the scope up the biliary limb

- Limited accessories

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Donor variation

Complete

Deceased donor liver (DD)

Donor after cardiac death (DCD)

- Increased risk of biliary complications vs DD

Partial Liver

Living donor transplant (LDLT)

- Right lobe

- Smaller duct caliber –increased complications vs DD

Split liver transplant (SLD)

- Left or right lobe

Sectoral Ductal Anatomy

Left hepatic duct sector

- II, III and IV

Right anterior sector

- V and VIII

Right posterior sector

- VI and VII

Diagnosis

Clinical suspicion early post-operatively

Asymptomatic – incidental finding on routine labs/imaging

Symptoms – pain, fever, jaundice, pruritis

Labs Elevated LFTs Signs of infection

Imaging Modalities

Ultrasound Nuclear medicine scan CT MRCP EUS ERCP PTC

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

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Imaging Modalities

Ultrasound Nuclear medicine scan CT MRCP EUS ERCP PTC

Ductal dilation on US, Doppler for vascular abnormalities

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

Imaging Modalities

Ultrasound Nuclear medicine scan CT MRCP EUS ERCP PTC

Biliary leak evaluation

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

Nuclear Medicine Hepatobiliary Scan

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Surgical Drain

Surgical Drain

Nuclear Medicine Hepatobiliary Scan

Surgical Drain

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Imaging Modalities

Ultrasound Nuclear medicine scan CT MRCP EUS ERCP PTC

Fluid collections/ abscesses

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

Imaging Modalities

Ultrasound Nuclear medicine scan CT MRCP EUS ERCP PTC

Main diagnostic study

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

MRCP (Magnetic Resonance Cholangiopancreatograpy)

• Non-invasive, non-contrast

• Evaluation of entire biliary tree

• Provides a roadmap of anatomy prior to intervention

• High sensitivity for determining strictures and stones

• Newer contrast media allows dynamic imaging of the biliary system

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

MRCP

Limitations

- Pacemaker/ICD

- Patient compliance, claustrophobia

- Small stones may be missed

- May falsely suggest stricture at anastomotic site

- Contrast MRI

Nephrogenic systemic sclerosis

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

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MRCP: Anastomotic stricture in LDLT

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Imaging Modalities

Ultrasound Nuclear medicine scan CT MRCP EUS ERCP PTC

Rarely done early, can be done to evaluate biliary/pancreatic diseases

Imaging Modalities

Ultrasound Nuclear medicine scan CT MRCP EUS ERCP PTC

Therapeutic procedures, should NOT be considered diagnostic studies

Biliary Strictures

Anastomotic

Short, focal stricture, at the bile duct anastomosis

Occur in 5-10 % of patients with deceased donor transplantation

Scarring and fibrosis

Non-anastomotic strictures

Upstream from biliary anastomosis, involve intrahepatic ducts/branches

Deceased Donor: 5-15%, Donor after cardiac death: 20-33%

Multiple etiologies - Ischemia plays a major role- Associated with HA stenosis/occlusion, PV occlusion, CMV, PSC, ABO incompatibility, chronic rejection

Arain MA et al. Liver Transpl 19:482–498, 2013, Koneru B. Liver Transpl 2006;12:702-704Duffy JP et al. Ann Surg 2010;252:652-661, Ayoub WS et al. Dig Dis Sci 2010;55: 1540-1546

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Biliary Strictures

Anastomotic

Respond well to endoscopic therapy

Non-anastomotic strictures

Difficult to treat

Require prolonged treatment often 12 months or more with multiple endoscopic procedures

Increased morbidity, decreasedgraft survival

Arain MA et al. Liver Transpl 2013, Koneru B. Liver Transpl 2006, Buxbaum JL et al GIE 2011 Duffy JP et al. Ann Surg 2010, Ayoub WS et al. Dig Dis Sci 2010

Anastomotic Stricture on MRCP

ERCP Balloon dilation of the stricture

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Multiple stents across the stricture High grade Anastomotic Stricture

No filling above the stricture initially

Wire passage across the stricture

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Proximal filling Balloon Dilation

Fully covered metal biliary stent

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Resolution

Principles of Stricture Management

Sphincterotomy → Balloon dilation → Stent placement

Repeat ERCP q2-3 months and place maximal number of large caliber stents (10 Fr) until stricture resolves

Consider fully covered metallic biliary stents for high grade, resistant strictures or as first line therapy - associated with fewer number of procedures* (two recent randomized trials)

Graziadei IW et al. Liver Transpl 2006, Rizk RS et al. Gastrointest Endosc 1998, Morelli J et al. Gastrointest Endosc2003, Costamagna G et al. Gastrointest Endosc 2001, *Cote G et al. JAMA 2016, *Tal AO et al. GIE 2017

ERCP early post-op, low platelets

Pancreatic duct cannulation

CBD stricture

Pancreatic duct stent

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Balloon dilation of the biliary orifice

Biliary stents

Pancreatic stent

Difficult Stricture: PTC aided treatment Percutaneous transhepatic balloon dilation

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Percutaneous transhepatic balloon dilation

Non-anastomotic Strictures Filling of all three sectoral ducts

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Balloon dilation: Right posterior hepatic duct Balloon dilation: Right anterior hepatic duct

Balloon dilation: left hepatic duct 10 Fr stents in all sectoral ducts

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Ischemic Cholangiopathy – 3 mo post Ischemic Cholangiopathy – 3 mo post

Ischemic Cholangiopathy – 3 mo post Ischemic Cholangiopathy – 3 mo post

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‘Resolution’ after 8 ERCPs… DCD complicated by HA stenosis

MRCP – Ischemic cholangiopathy

Central scarring extending into the intrahepatic branches

No specific target for endoscopic therapy

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Post-transplant Bile Leaks

Up to 25% of patients

Etiology

- Anastomotic site leak

- Ischemic injury

- T-tube insertion (if done)

- Surface leak

Associated with fluid collections, abscesses

Generally, respond to intensive endoscopic therapy

- however, high rate of PTC and surgery reported in the literature

Arain MA et al. Liver Transpl 19:482–498, 2013, Koneru B. Liver Transpl 2006;12:702-704Duffy JP et al. Ann Surg 2010;252:652-661, Ayoub WS et al. Dig Dis Sci 2010;55: 1540-1546

Bile leak – Duct to duct anastomosis

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Bile leak – Duct to duct anastomosis

Pancreatic wire

Percutaneous drainCBD

Bile leak – Duct to duct anastomosis

Anastomotic leak

Bile leak – Duct to duct anastomosis

CBD and PD stents

Biliary Leak

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Principles of Anastomotic Leak Management

Sphincterotomy (assuming no contraindication) → Avoid balloon dilation → Stent placement across the leak

Repeat ERCP in 4-6 weeks and upsize stent(s) and/or place additional stents (if possible)

May develop stricture at the leak site – dilation okay once leak resolves

Graziadei IW et al. Liver Transpl 2006, Rizk RS et al. Gastrointest Endosc 1998, Morelli J et al. Gastrointest Endosc2003, Costamagna G et al. Gastrointest Endosc 2001

Stones and Casts

Bile Stasis Stone formation

Biliary strictures lead to stasis … there similar risk factors for stone formation as strictures (arterial/venous compromise, ischemia etc)

NAS Recurrent intrahepatic stones/casts

Casts syndrome – multiple large, hard stones, often hilar/central ductal dilation, longstanding impairment of flow vs different etiology?

Stones on MRCP

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Biliary Casts Endoscopy in Altered anatomy

Roux-en-Y hepaticojejunostomy (RYHJ)

Enteroscopy assisted ERC

- Pediatric colonoscope

- Device assisted (single balloon or double balloon enteroscopy)

Roux-en-Y gastric bypass (RYGB)

Enteroscopy

Remnant access Percutaneous, EUS-guided or surgical access

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Deep Enteroscopy : Single balloon overtube assisted

Stenotic anastomosis Cannulation

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Balloon dilation Living Donor Liver Transplantation

Difficult anastomoses due to small size of donor ducts

Higher incidence of ischemic and non-ischemic complications

A2ALL – multi-center US cohort

- Recipient: Leak 32%, Stricture 17%

- Donor: Leak 9.2%, Stricture 0.7%

Olthoff KM et al. Ann Surg 2005, Ghobrial RM et al. Gastroenterology 2008, Soejima Y et al. Liver Transpl 2006, Seo JK et al. Liver Transpl 2009

Living Donor Liver Transplantation

Management

- Biliary strictures – Response 60-80%...low

- Biliary leaks – Need for surgery 50-65%...high

- High rates of PTC and surgery for both…really necessary?

Olthoff KM et al. Ann Surg 2005, Ghobrial RM et al. Gastroenterology 2008, Soejima Y et al. Liver Transpl 2006, Seo JK et al. Liver Transpl 2009, Rao HB et al WJG 2018

MRCP:Anastomotic stricture in LDLT

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Right anterior and posterior sectoral access

Balloon dilation Bisectoral stent placement

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Follow-up ERCP Additional stent placement into right anterior duct

Resolution of strictures LDLT with early anastomotic leak

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Small intrahepatic ducts Bisectoral access

Bisectoral 5 Fr stents Follow-up ERCP

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7 Fr and 8.5 Fr stents Resolution of leak

Leak with fistula and abscess Gastric fistula to the abscess cavity

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Balloon dilation of fistula tract and transpapillary stent into the abscess Cavity sweep/lavage with a stone retrieval balloon

Multiple stents

Transgastricstent into cavity

Transpapillarystent into cavity

Transpapillarybiliary stent

Resolution (months later)

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LDLT leak – Anastomotic variation

Cystic duct to right posterior

Hepatic duct to right anterior

Right anterior duct anastomotic leak

Cystic duct to right posterior

Hepatic duct to right anterior

Leak

Dual stents Resolution of leak

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Right LDLT with RYHJ Enteroscopy ERC Right LDLT Anterior duct wire

Posterior duct wire

Stents after balloon dilation

Anterior duct stent

Posterior duct stent

Donor Leak

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Dual stents – 10 Fr long and short Resolution of leak

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Complication Recurrence

13/46 (28%) pts

All were biliary strictures

Median duration from stent removal to presentation: 3.7 months (0.7-19.3)

12/13 treated with repeat ERCP

- Median # of ERCPs: 4 (range 2-9)

- No PTC or surgery

- 1 pt lost to follow-up

Advances in ERCP Technology

Access

- SwingTip, bidirectional, steerable cannula

- Wide array of wires (Visiglide, NovaGold, Terumo Glide)

Therapy

- Soft large caliber stents (Johlin)

- Covered metal biliary stents

Cholangioscopy

- Direct using a pediatric endoscope

- SpyGlass -> SpyGlass DS (fiber optic vs digital)

Conclusions

Biliary complications are common post LT

Non-invasive diagnostic imaging (MRCP, HIDA) should precede therapeutic endoscopy

Advanced endoscopists must be knowledgeable in biliary anatomy and be aware of the patient’s type of transplant and ductal anatomy

Advances in endoscopic technologies and development of newer accessories allow a high proportion (ideally over 90%) of patients to be treated endoscopically

Duration of therapy varies depending on underlying etiology e.g. type of donor liver, vascular complications etc.

Patients require a multi-disciplinary approach to co-manage complications (e.g. leaks) and/or facilitate endoscopic treatment (e.g. difficult access)

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