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Interventional Case Record
Interventional Case Record
Stenting of hepatic vein stenosis following deceased donor liver transplantation in Wilson disease : Rejection is not always the whole story
Stenting of hepatic vein stenosis following deceased donor liver transplantation in Wilson disease : Rejection is not always the whole story
Contributed by : Onkar Kanagi
Contributed by : Onkar Kanagi
Wilson disease is named after Samuel Alexander Kinnier Wilson (1878–1937), an American-born British neurologist. He described the condition in detail in 1912 in his postgraduate MD thesis at the University of Edinburgh, which was subsequently published in the journal Brain. He titled the paper "Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver", establishing the link between the neurological symptoms and hepatic pathology.
Introduction:
Introduction:
Hepatic venous outflow obstruction (HVOO) is a recognized, butoften underdiagnosed, complication following liver transplantation, particularly in paediatric populations. Although relatively rare - with reported incidences of less than 2% in adult series and higher rates in paediatric and split-liver transplants, HVOO can have significant implications for graft function and patient outcomes. The pathophysiology involves stenosis or thrombosis at the site of anastomosis of hepatic vein or in intrahepatic venous channels, leading to impaired outflow, hepatic congestion, and subsequent graft dysfunction.
Hepatic venous outflow obstruction (HVOO) is a recognized, butoften underdiagnosed, complication following liver transplantation, particularly in paediatric populations. Although relatively rare - with reported incidences of less than 2% in adult series and higher rates in paediatric and split-liver transplants, HVOO can have significant implications for graft function and patient outcomes. The pathophysiology involves stenosis or thrombosis at the site of anastomosis of hepatic vein or in intrahepatic venous channels, leading to impaired outflow, hepatic congestion, and subsequent graft dysfunction.
Clinically, HVOO presents with signs of graft congestion such as hepatomegaly, ascites, pleural effusion, and abnormal liver function tests. Doppler ultrasonography is a frontline screening tool. It shows loss of normal triphasic waveforms and monophasic patterns serving as key indicators of outflow impairment. Cross-sectional imaging, particularly contrast-enhanced CT scans, complement Doppler studies by delineating anatomical abnormalities and excluding thrombosis or other surgical complications.
Clinically, HVOO presents with signs of graft congestion such as hepatomegaly, ascites, pleural effusion, and abnormal liver function tests. Doppler ultrasonography is a frontline screening tool. It shows loss of normal triphasic waveforms and monophasic patterns serving as key indicators of outflow impairment. Cross-sectional imaging, particularly contrast-enhanced CT scans, complement Doppler studies by delineating anatomical abnormalities and excluding thrombosis or other surgical complications.
The definitive diagnosis relies on hepatic venography with pressure gradient measurement, with a trans-stenotic gradient of approximately 6 mm Hg or more being a threshold for intervention. Treatment options include balloon venoplasty and stent placement, with the latter often favoured in cases of fixed or recurrent stenosis due to its durability.
The definitive diagnosis relies on hepatic venography with pressure gradient measurement, with a trans-stenotic gradient of approximately 6 mm Hg or more being a threshold for intervention. Treatment options include balloon venoplasty and stent placement, with the latter often favoured in cases of fixed or recurrent stenosis due to its durability.
This case underscores the importance of maintaining a high index of suspicion for vascular complications in post-transplant patients, especially when graft dysfunction persists despite treatment of rejection. Recognizing and managing hepatic venous outflow obstruction promptly can significantly improve graft survival and patient outcome, emphasizing the need for a multidisciplinary approach integrating clinical, radiologic, and interventional expertise.
This case underscores the importance of maintaining a high index of suspicion for vascular complications in post-transplant patients, especially when graft dysfunction persists despite treatment of rejection. Recognizing and managing hepatic venous outflow obstruction promptly can significantly improve graft survival and patient outcome, emphasizing the need for a multidisciplinary approach integrating clinical, radiologic, and interventional expertise.
Case presentationm
Case presentationm
A nine-year-old boy with genetically proven Wilson disease (ATP7B homozygous mutation positive) presented with acute-on-chronic liver failure and had previously undergone two sessions of plasmapheresis before liver transplantation . His pre-transplant course was further complicated by suspected fungal sepsis, with markedly positive beta-D-glucan and galactomannan, treated with micafungin with subsequent clinical and serologic improvement.
A nine-year-old boy with genetically proven Wilson disease (ATP7B homozygous mutation positive) presented with acute-on-chronic liver failure and had previously undergone two sessions of plasmapheresis before liver transplantation . His pre-transplant course was further complicated by suspected fungal sepsis, with markedly positive beta-D-glucan and galactomannan, treated with micafungin with subsequent clinical and serologic improvement.
He underwent deceased donor liver transplantation (DDLT). The early postoperative course was complicated by persistent fever, hypotension, and progressive graft dysfunction.
He underwent deceased donor liver transplantation (DDLT). The early postoperative course was complicated by persistent fever, hypotension, and progressive graft dysfunction.
Early post-transplant course
Early post-transplant course
During the first few postoperative days:
During the first few postoperative days:
POD 1: Persistent fever and hypotension led to escalation of antibiotics and continuation of hydrocortisone.
POD 1: Persistent fever and hypotension led to escalation of antibiotics and continuation of hydrocortisone.
POD 3: Inotropes were stopped and tacrolimus with methylprednisolone was initiated.
POD 3: Inotropes were stopped and tacrolimus with methylprednisolone was initiated.
POD 7 onward: Liver enzymes rose again, prompting concern for rejection. (Table 1)
POD 7 onward: Liver enzymes rose again, prompting concern for rejection. (Table 1)
Table 1: Table 1: Laboratory investigations. AST = Aspartate aminotransferase; ALT = Alanine aminotransferase; ALP = Alkaline phosphatase; MPS=Methylprednisolone.Steroid escalation produced only transient biochemical improvement.
A percutaneous transplant liver biopsy was performed in the early postoperative period. Histopathology was reviewed as plasma cell-rich rejection, with C4d score 3, supporting a diagnosis of mixed severe rejection with antibody-mediated rejection (AMR) and T-cell mediated rejection (TCMR).
A percutaneous transplant liver biopsy was performed in the early postoperative period. Histopathology was reviewed as plasma cell-rich rejection, with C4d score 3, supporting a diagnosis of mixed severe rejection with antibody-mediated rejection (AMR) and T-cell mediated rejection (TCMR).
Therefore, the patient was treated with:
Therefore, the patient was treated with:
pulse methylprednisolone
pulse methylprednisolone
optimization of tacrolimus
optimization of tacrolimus
plasmapheresis
plasmapheresis
Following the treatment liver enzymes decreased. (Table 1)
Following the treatment liver enzymes decreased. (Table 1)
Radiological clues suggesting that this was more than simple case of rejection are as follows.
Radiological clues suggesting that this was more than simple case of rejection are as follows.
Although rejection was clearly present, the imaging pattern suggested that rejection alone might not explain the full picture.
Although rejection was clearly present, the imaging pattern suggested that rejection alone might not explain the full picture.
Serial Doppler studies after transplant showed:
Serial Doppler studies after transplant showed:
• Persistent monophasic waveform in left and middle hepatic veins.
• Persistent monophasic waveform in left and middle hepatic veins.
• High flow velocities across the IVC/anastomotic region
• High flow velocities across the IVC/anastomotic region
• Mild ascites
• Mild ascites
• Heterogeneous graft echotexture
• Heterogeneous graft echotexture
Selected Doppler findings from the record included:
Selected Doppler findings from the record included:
• POD 2: Middle hepatic vein monophasic flow; Left hepatic vein biphasic flow; elevated PSV at the IVC anastomotic site.
• POD 2: Middle hepatic vein monophasic flow; Left hepatic vein biphasic flow; elevated PSV at the IVC anastomotic site.
• POD 3 to POD 6: Persistent monophasic flow in the left hepatic vein, with elevated PSV at the IVC anastomosis and persistent small-volume free fluid.
• POD 3 to POD 6: Persistent monophasic flow in the left hepatic vein, with elevated PSV at the IVC anastomosis and persistent small-volume free fluid.
• POD 12: Continued monophasic hepatic venous waveform, raised PSV at IVC anastomotic site and heterogenous liver echotexture.
• POD 12: Continued monophasic hepatic venous waveform, raised PSV at IVC anastomotic site and heterogenous liver echotexture.
At this stage, CECT was performed. This however showed no thrombosis or major abnormality. Therefore graft dysfunction was initially managed as predominantly rejection-related.
At this stage, CECT was performed. This however showed no thrombosis or major abnormality. Therefore graft dysfunction was initially managed as predominantly rejection-related.
In view of raised liver enzymes, the patient was readmitted. He underwent ultrasonography guided liver biopsy.
In view of raised liver enzymes, the patient was readmitted. He underwent ultrasonography guided liver biopsy.
Around this period, laboratory values continued to show features of graft dysfunction, with AST 145 IU/L, ALT 228 IU/L, total bilirubin 1.4 mg/dL, albumin 3.4 g/dL and platelets 84,000/mm3.
Around this period, laboratory values continued to show features of graft dysfunction, with AST 145 IU/L, ALT 228 IU/L, total bilirubin 1.4 mg/dL, albumin 3.4 g/dL and platelets 84,000/mm3.
Repeat biopsy proved to be the major turning point in the case as it showed no evidence of inflammation/fibrosis. Rather it showed severe sinusoidal congestion . This shifted the diagnostic focus toward a venous outflow problem.
Repeat biopsy proved to be the major turning point in the case as it showed no evidence of inflammation/fibrosis. Rather it showed severe sinusoidal congestion . This shifted the diagnostic focus toward a venous outflow problem.
Subsequently, hepatoportal Doppler. This showed :
Subsequently, hepatoportal Doppler. This showed :
• Short segment narrowing of intrahepatic IVC at anastomotic site with raised PSV.
• Short segment narrowing of intrahepatic IVC at anastomotic site with raised PSV.
• Dilated middle and left hepatic veins with ostial narrowing and monophasic waveform.
• Dilated middle and left hepatic veins with ostial narrowing and monophasic waveform.
Radiological investigations:
Radiological investigations:
CECT of the abdomen confirmed the diagnosis of middle and left hepatic vein ostial stenosis establishing that the patient had developed hepatic venous outflow obstruction in addition to severe rejection. (Fig 1,2, 3).
CECT of the abdomen confirmed the diagnosis of middle and left hepatic vein ostial stenosis establishing that the patient had developed hepatic venous outflow obstruction in addition to severe rejection. (Fig 1,2, 3).
Figure 1
Figure 2
Figure 3
Figure 1: Axial contrast enhanced CT image showing narrowing at LHV and MHV ostium.
Figure 2:Coronal contrast enhanced CT image showing narrowing at LHV ostium.
Figure 3: Coronal contrast enhanced CT image showing narrowing at MHV ostium.
A diagnosis of post-transplant hepatic vein stenosis with hepatic venous outflow obstruction, occurring in the background of severe mixed rejection (AMR + TCMR) after DDLT for Wilson disease was made.
A diagnosis of post-transplant hepatic vein stenosis with hepatic venous outflow obstruction, occurring in the background of severe mixed rejection (AMR + TCMR) after DDLT for Wilson disease was made.
Interventional Technique
Interventional Technique
In view of the biochemical and radiological findings described above, the patient was posted for hepatic venography with measurement of pressure gradient across stenosis and, if required, HV stenting.
In view of the biochemical and radiological findings described above, the patient was posted for hepatic venography with measurement of pressure gradient across stenosis and, if required, HV stenting.
The procedure was performed under General anaesthesia with all aseptic precautions.
The procedure was performed under General anaesthesia with all aseptic precautions.
Right internal jugular vein access was obtained using a 8 Fr sheath
Right internal jugular vein access was obtained using a 8 Fr sheath
Left internal jugular vein access was also obtained using 6 Fr sheath.
Left internal jugular vein access was also obtained using 6 Fr sheath.
Selective catheterization of middle hepatic vein and left hepatic vein was performed using Terumo wire and MPA catheter. Trans-stenotic pressure gradient was obtained across the stenotic segments in middle hepatic vein and left hepatic vein.
Selective catheterization of middle hepatic vein and left hepatic vein was performed using Terumo wire and MPA catheter. Trans-stenotic pressure gradient was obtained across the stenotic segments in middle hepatic vein and left hepatic vein.
Trans-stenotic pressure gradient across stenotic segments in both hepatic veins was approximately 4 mmHg.
Trans-stenotic pressure gradient across stenotic segments in both hepatic veins was approximately 4 mmHg.
Hepatic venogram revealed focal shorth segmental stenosis at the ostium of middle hepatic vein and left hepatic vein. (Fig 4 - 7)
Hepatic venogram revealed focal shorth segmental stenosis at the ostium of middle hepatic vein and left hepatic vein. (Fig 4 - 7)
igure 4: Image showing minimal narrowing of intrahepatic IVC.
Figure 5: iIage showing narrowing at ostium of LHV.
Figure 6 : Image showing narrowing at ostium of MHV.
Figure 7: Image showing narrowing at ostium of MHV and LHV.
The left hepatic vein was crossed using a stiff wire and a 10mm x 27mm balloon mounted stent was deployed across the left hepatic vein ostium. (Fig 8)
The left hepatic vein was crossed using a stiff wire and a 10mm x 27mm balloon mounted stent was deployed across the left hepatic vein ostium. (Fig 8)
Figure 8: Image showing showing ballon mounted stent placed across LHV stenosis.
Figure 9: Image showing significant luminal gain and good flow of contrast across LHV post stenting.
The middle hepatic vein was crossed with V18 wire and pre-dilatation was done using 5mm and 6mm balloons. (Fig 10)
The middle hepatic vein was crossed with V18 wire and pre-dilatation was done using 5mm and 6mm balloons. (Fig 10)
Post dilatation, a 10mm x 25mm balloon mounted stent was deployed across the middle hepatic vein ostium. (Fig 11)
Post dilatation, a 10mm x 25mm balloon mounted stent was deployed across the middle hepatic vein ostium. (Fig 11)
Post procedural venogram revealed good luminal gain with good flow of contrast across middle hepatic vein and left hepatic vein. (Fig 9 & 12)
Post procedural venogram revealed good luminal gain with good flow of contrast across middle hepatic vein and left hepatic vein. (Fig 9 & 12)
Figure 10
Figure 11
Figure 12
Figure 10:Image showing pre-dilatation of MHV done using 5mm balloon.
Figure 11: Image showing ballon mounted stent placed across MHV stenosis.
Figure 12: Post-stenting Image showing significant luminal gain and good flow of contrast across MHV
Discussion
Discussion
Post-transplant venous outflow obstructionin liver transplants is rare, but clinically significant, and reported incidence varies by graft type and anastomotic technique. Reviews describe it as less than 2% overall in many adult series, while paediatric split graft series report higher rates in selected anatomies. [1]
Post-transplant venous outflow obstructionin liver transplants is rare, but clinically significant, and reported incidence varies by graft type and anastomotic technique. Reviews describe it as less than 2% overall in many adult series, while paediatric split graft series report higher rates in selected anatomies. [1]
Typical manifestations include ascites, pleural effusion, hepatic congestion, abnormal liver tests, and dampening of hepatic venous waveforms to a monophasic pattern on Doppler. [2]
Typical manifestations include ascites, pleural effusion, hepatic congestion, abnormal liver tests, and dampening of hepatic venous waveforms to a monophasic pattern on Doppler. [2]
CT can show short-segment focal anastomotic narrowing with prestenotic dilatation, while Doppler may show monophasic flow in the affected hepatic vein. [3]
CT can show short-segment focal anastomotic narrowing with prestenotic dilatation, while Doppler may show monophasic flow in the affected hepatic vein. [3]
Venography remains the key confirmatory investigation because it allows both visualization of the stenosis and measurement of a trans-stenotic pressure gradient. In the imaging literature, a gradient of around 6 mm Hg or more has been described as clinically significant and used as a threshold supporting intervention in hepatic vein stenosis. [3]
Venography remains the key confirmatory investigation because it allows both visualization of the stenosis and measurement of a trans-stenotic pressure gradient. In the imaging literature, a gradient of around 6 mm Hg or more has been described as clinically significant and used as a threshold supporting intervention in hepatic vein stenosis. [3]
In paediatric transplant literature, venous outflow obstruction is a major graft-threatening complication. In one recent paediatric split-liver series, venous outflow obstruction occurred in 8.6% of transplants, and percutaneous transluminal angioplasty restored outflow in most cases. [4]
In paediatric transplant literature, venous outflow obstruction is a major graft-threatening complication. In one recent paediatric split-liver series, venous outflow obstruction occurred in 8.6% of transplants, and percutaneous transluminal angioplasty restored outflow in most cases. [4]
Endovascular therapy is considered the first-line in most post-transplant venous outflow lesions. Balloon angioplasty can be effective, but recurrent or fixed lesions often require stent placement for durable decompression. Paediatric reports also note that restenosis may require repeated interventions if stenting is deferred.
Endovascular therapy is considered the first-line in most post-transplant venous outflow lesions. Balloon angioplasty can be effective, but recurrent or fixed lesions often require stent placement for durable decompression. Paediatric reports also note that restenosis may require repeated interventions if stenting is deferred.
Why this case is important:
Why this case is important:
This case is important because it illustrates a classic but easily missed problem in transplant medicine:
This case is important because it illustrates a classic but easily missed problem in transplant medicine:
Biopsy-proven rejection does not exclude a simultaneous vascular complication.
Biopsy-proven rejection does not exclude a simultaneous vascular complication.
In this child, the early course strongly supported rejection, but the persistence of abnormal graft function, repeated abnormal hepatic venous waveforms, and later biopsy evidence of congestion pointed toward a second pathology. CT then confirmed hepatic vein stenosis, and definitive management required endovascular stenting.
In this child, the early course strongly supported rejection, but the persistence of abnormal graft function, repeated abnormal hepatic venous waveforms, and later biopsy evidence of congestion pointed toward a second pathology. CT then confirmed hepatic vein stenosis, and definitive management required endovascular stenting.
This is the main teaching message: persistent graft dysfunction after treatment of rejection should trigger renewed evaluation for hepatic venous outflow obstruction.
This is the main teaching message: persistent graft dysfunction after treatment of rejection should trigger renewed evaluation for hepatic venous outflow obstruction.
Key teaching points:
Key teaching points:
• Do not anchor on rejection alone. Even proven AMR/TCMR may coexist with a mechanical vascular lesion.
• Do not anchor on rejection alone. Even proven AMR/TCMR may coexist with a mechanical vascular lesion.
• Persistent monophasic hepatic venous waveform matters. In the right clinical context, it should raise suspicion for hepatic venous outflow obstruction.
• Persistent monophasic hepatic venous waveform matters. In the right clinical context, it should raise suspicion for hepatic venous outflow obstruction.
• Biopsy showing congestion is a major clue. Congestion on histology should prompt reassessment of venous drainage.
• Biopsy showing congestion is a major clue. Congestion on histology should prompt reassessment of venous drainage.
• CT and Doppler are complementary. Doppler raises suspicion; CT defines anatomy; venography confirms hemodynamic significance and enables treatment.
• CT and Doppler are complementary. Doppler raises suspicion; CT defines anatomy; venography confirms hemodynamic significance and enables treatment.
• Endovascular treatment is central. Balloon venoplasty may suffice in some patients, but stenting is often needed when stenosis is fixed, severe, or recurrent.
• Endovascular treatment is central. Balloon venoplasty may suffice in some patients, but stenting is often needed when stenosis is fixed, severe, or recurrent.
References
References
1. Pinelli D, Sansotta N, Cavallin F, et al. Venous outflow obstruction in paediatric left lateral segment split liver transplantation. Clin Transplant. 2023;37:e14985. https://doi.org/10.1111/ctr.14985.
1. Pinelli D, Sansotta N, Cavallin F, et al. Venous outflow obstruction in paediatric left lateral segment split liver transplantation. Clin Transplant. 2023;37:e14985. https://doi.org/10.1111/ctr.14985.
2. Value of CT and Doppler Sonography in the Evaluation of Hepatic Vein Stenosis After Dual-Graft Living Donor Liver Transplantation; Seung Soo Lee, Kyoung Won Kim, Seong Ho Park, Yong Moon Shin, Pyo Nyun Kim, Sung Gyu Lee, and Moon-Gyu Lee.
2. Value of CT and Doppler Sonography in the Evaluation of Hepatic Vein Stenosis After Dual-Graft Living Donor Liver Transplantation; Seung Soo Lee, Kyoung Won Kim, Seong Ho Park, Yong Moon Shin, Pyo Nyun Kim, Sung Gyu Lee, and Moon-Gyu Lee.
3. Gonzalez A, Cooper E, Herren J, Lipnik AJ, Xie KL. Diagnostic and Interventional Radiology in the Management of Post-Liver Transplant Vascular Complications. Semin Intervent Radiol. 2022 Dec 20;39(5):537-544. doi: 10.1055/s-0042-1758113. PMID: 36561931; PMCID: PMC9767772.
3. Gonzalez A, Cooper E, Herren J, Lipnik AJ, Xie KL. Diagnostic and Interventional Radiology in the Management of Post-Liver Transplant Vascular Complications. Semin Intervent Radiol. 2022 Dec 20;39(5):537-544. doi: 10.1055/s-0042-1758113. PMID: 36561931; PMCID: PMC9767772.
4. Kwong A J, Kim W R, Lake J R. OPTN/SRTR 2019 Annual Data Report: liver. Am J Transplant. 2021;21 02:208–315. doi: 10.1111/ajt.16494. [DOI] [PubMed] [Google Scholar]
4. Kwong A J, Kim W R, Lake J R. OPTN/SRTR 2019 Annual Data Report: liver. Am J Transplant. 2021;21 02:208–315. doi: 10.1111/ajt.16494. [DOI] [PubMed] [Google Scholar]
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