Outcomes of transjugular liver biopsies for liver transplant recipients with bicaval and piggyback hepatic vein anastomoses

Abstract

Background

Liver transplant hepatic venous anastomoses are usually created using “bicaval” or “piggyback” techniques, which may result in unfavorable angulation between the inferior vena cava and hepatic veins, and makes hepatic vein catheterization and tissue sampling during transjugular liver biopsy (TLB) technically challenging.

Purpose

To compare the technical successes and complications of TLBs for recipients of liver transplants with bicaval and piggyback hepatic vein anastomoses.

Material and Methods

Information on type of hepatic vein surgical anastomosis was available for 190 adult patients in whom 306 consecutive TLBs were performed during 2009–2017: 158 with bicaval and 148 with piggyback anastomoses. The primary outcome of procedural success was defined as obtaining a tissue sample sufficient to make a pathologic diagnosis.

Results

A technical success rate of 97% with adequate liver tissue for diagnosis was similar between the anastomotic groups (P = 0.50). TLB was unsuccessful in 3% of patients with piggyback anastomoses due to unfavorable hepatic venous anatomy whereas biopsy was successful in all patients with bicaval anastomoses (P = 0.02). Fluoroscopy times were not significantly different (12.1 vs. 13.9 min, P = 0.08). Rates of major complication were similar between the two groups (3% vs. 3%, P > 0.99).

Conclusion

TLB is safe and effective for liver transplant patients regardless of the type of hepatic vein anastomosis. While failure to catheterize or advance the stiffened biopsy cannula into the hepatic vein is more likely to occur in patients with piggyback anastomoses, this is a rare occurrence.

Keywords

Transjugular liver biopsy hepatic vein anastomosis bicaval piggyback

Introduction

Percutaneous liver biopsy is contraindicated for patients with coagulopathy, ascites, or no safe percutaneous window, and transjugular liver biopsy provides a safe alternative (1 –6). Transjugular liver biopsy also allows for hepatic venography and hepatic manometry. Hepatic manometry offers the ability to measure the portal-systemic and hepatic venous pressure gradients, which are surrogates for clinical endpoints in patients with chronic liver disease (7 –9).

Previous studies suggest that transjugular biopsy has high rates of technical success and adequate sampling (10,11). The most common reason cited for technical failure is inability to cannulate the hepatic veins, a challenge made more difficult in patients with surgically altered anatomy (10,12,13).

Two different types of anastomoses, termed “bicaval” and “piggyback,” are commonly used to connect donor hepatic veins with the recipient inferior vena cava (IVC) in whole liver orthotopic liver transplantation (OLT) (Figs. 1 and 2). While OLT was originally described with the bicaval anastomotic technique, the piggyback technique allows surgeons to preserve blood return from the lower extremities during the procedure, is often required for living donor grafts, and can shorten warm ischemia time because it requires fewer anastomoses (14,15). Living donor liver transplant (LDLT) anastomosis require an end-to-side anastomosis of donor hepatic veins with the recipient IVC, forming angles which are similar in nature to whole liver OLT with piggyback anastomosis.

Fig. 1.

(a) Schematic drawing of a bicaval anastomosis. Surgical technique requires complete interruption of blood return from the lower extremities through the IVC. (b) A digital subtraction venogram from transjugular biopsy in a patient with a bicaval anastomosis shows a favorable angle between the hepatic veins and the IVC. The access cannula is within the right hepatic vein. IVC, inferior vena cava.

Fig. 2.

(a) Schematic drawing of a piggyback anastomosis. During transplantation this anastomotic technique allows preservation of blood return from the lower extremities through the IVC. The resulting angle between the hepatic veins and the IVC can render hepatic vein selection more challenging. (b) A digital subtraction venogram from transjugular biopsy in a patient with a piggyback anastomosis shows an unfavorable angle between the hepatic veins and the IVC. The access cannula is within the right hepatic vein. IVC, inferior vena cava.

Prior research regarding the effect of hepatic vein anastomosis technique on transjugular biopsy outcomes has been limited to a single-center retrospective study that suggested that piggyback surgical anastomosis was associated with a lower likelihood of obtaining sufficient tissue during transjugular liver biopsies versus bicaval anastomosis (93% vs. 98%). The difference was primarily due to the failure in cannulating the hepatic veins in 4% of patients in the piggyback group compared to 0.8% of patients in the bicaval group (16).

Piggyback venous anastomoses may result in an unfavorable angulation between the inferior vena cava and the target hepatic vein, which could, in turn, lower the chances of successful hepatic vein catheterization, prevent passage of the stiffened guiding cannula, and reduce the ability to obtain an adequate tissue sample. Increased technical difficulty may result in longer procedure fluoroscopy time and increase chances of a complication. The aim of the present study was to compare technical success rates, differences in anatomic appearance, and complications of transjugular liver biopsies performed for recipients of liver transplants with piggyback and bicaval hepatic venous anastomoses.

Material and Methods

This retrospective single-center study was approved by the Institutional Review Board and was compliant with the Health Insurance Portability and Accountability Act of 1996. The informed consent requirement was waived. Electronic medical records (EMR) (Epic Systems Corporation, Verona, WI, USA) of all consecutive liver transplant recipients who had undergone transjugular liver biopsy procedures between September 2009 and December 2017 were retrospectively reviewed (Fig. 3). Eleven patients were excluded from the study because the type of hepatic vein anastomosis was not documented in the EMR. Among 190 patients with operative reports available, three had a second transplant during the study period, for which nine biopsies were performed. These nine biopsy procedures were excluded from the data analysis to reduce confounding. A team of eight fellowship-trained, full-time interventional radiologists with 2–30 years of procedural experience performed the biopsies. All procedures were performed in a digital fluoroscopy suite using a Liver Access and Biopsy Set and a 19-gauge Quick Core cutting-style biopsy needle (Cook Inc., Bloomington, IN, USA).

Fig. 3.

Flowchart of patient inclusion and exclusion.

To perform the transjugular liver biopsy, ultrasound-guided venous access was first obtained, typically via the right internal jugular vein, and a 10-Fr angled sheath (Flexor® Check-Flo® 2 Introducer Set, 35 cm; Cook, Inc., Bloomington, IN, USA) was inserted. Right atrial and IVC pressures were measured via the 10-Fr sheath. Manometry was part of the standard transjugular biopsy technique. Pressures were measured with a pressure transducer (ICU Medical Inc., San Clemente, CA, USA). One of the hepatic veins was then accessed using an angled 5-Fr catheter, typically Multi-purpose type B (Cook, Inc.) or Cobra 2 (Cook, Inc.). The Multi-purpose type B catheter has a near 90° angle at the tip (angle tip length = 3 cm), while the Cobra 2 catheter has a “C-shaped” curve. Digital subtraction venography was performed via a hand injection through the 5-Fr angiographic catheter in the anteroposterior projection in order to document the size and location of the target hepatic vein using iodinated contrast. The right, middle, and left hepatic veins were identified based on venography appearance compared to pre-procedural cross-sectional imaging, if available, and a steep right anterior oblique image to determine the anteroposterior relationship of the tip of the catheter compared to the hepatic vein confluence. CO₂ was used for patients with renal insufficiency utilizing a handheld 60-mL Luer-lock syringe connected to a 99.9% pure CO₂ pressurized aluminum cylinder via a three-way stopcock and extension tubing. The 60-mL syringe was purged three times to ensure there was no air contamination and a volume of 20–30 mL of CO₂ was delivered over 2 s. Wedged CO₂ hepatic venography was not performed. The right hepatic vein was typically preferred for access, except for patients with a split liver allograft. After measuring free hepatic venous pressure through the 7-Fr balloon occlusion catheter (Boston Scientific, Natick, MA, USA), the balloon of the occlusion catheter was inflated with dilute contrast medium to measure the wedged hepatic pressure that represents the pressure transmitted from the portal vein through the sinusoids. Pressure measurements for the right atrium, IVC, free hepatic vein, and wedged hepatic vein were included in the procedure report, and these data were integrated by the referring physician in conjunction with the pathologic report to determine a diagnosis. The 10-Fr angled access sheath was then advanced into the hepatic vein for stability of access over a super stiff 0.035-inch guidewire (Amplatz, Boston Scientific, Inc.) either using the sheath introducer or the 7-Fr occlusion balloon for support. Next, the Check-Flo performer Assembly 7-Fr with 14-gauge stiffening cannula was inserted into the hepatic vein over a 0.035-inch super stiff guidewire. After removing the wire, the 19-gauge biopsy needle was introduced through the stiffened angled canula to perform the biopsy. The 7-Fr stiffened angled cannula was torqued anteriorly from the right hepatic vein and posteriorly from the middle hepatic vein in order to avoid puncturing the liver capsule. Intra-procedural evaluation of sample adequacy was qualitative. Additional needle passes beyond the first 2–3 were performed if the specimens were deemed insufficient by the interventional radiologist performing the procedure. This biopsy technique was utilized for all patients in the study and was also employed for patients with non-transplanted livers at our institution. Severe thrombocytopenia (platelet count < 50,000/µL) and/or coagulopathy (international normalized ratio for prothrombin time [INR] > 1.5) were corrected before the procedure to a goal platelet count of 50,000/µL and INR of 1.5. Platelet and INR levels were rarely checked following transfusion of blood products. Patients with platelet levels of 40,000–49,000 per µL received 1 unit of platelets, and patients with a platelet level of 24,000–39,000 per µL received 2 units of platelets. Patients with an INR in the range of 1.6–1.8 received 1 unit of fresh frozen plasma (FFP), while patients with an INR in the range of 1.9–2.1 (there were no patients with INR > 2.1) received 2 units of FFP.

The primary outcome was procedural success, defined as obtaining a tissue sample sufficient to make a pathologic diagnosis. If the pathologist could not render a diagnosis due to inadequate or non-target tissue, the procedure was considered a procedural failure. Secondary outcomes were number of portal tracts observed on the obtained biopsy specimen, major complications, and fluoroscopy time. Fluoroscopy time was defined as the time interval of fluoroscopy between the jugular access and withdrawal of catheter and sheath.

Operative reports were reviewed to determine type of liver transplant (whole or partial liver) and type of anastomosis (bicaval or piggyback). For the purposes of this analysis, whole liver OLT with piggyback anastomosis, partial liver cadaveric grafts, and LDLT were grouped together because of similar anastomotic configuration from an angiographic perspective when compared to whole liver OLTs with bicaval anastomosis. Interventional radiology reports were reviewed to determine whether a tissue sample was obtained and fluoroscopy times. Fluoroscopy data were not universally available due to changes in government-mandated reporting guidelines during the study period (17). Pathologists at our institution evaluated tissue specimen adequacy for pathologic diagnosis. The pathologic diagnosis of liver disease is made by examining the portal tracts, with the number of complete tracts being the crucial determinant of sample adequacy. This information was available in pathology reports and recorded for 269 of 296 procedures (91%) that yielded liver tissue adequate for pathologic diagnosis. Whether a sample contained six or more portal tracts, a previously cited threshold for transjugular liver biopsy sample adequacy (18) was also recorded. The medical record was reviewed for demographic information and for major and minor complications as defined by the Society of Interventional Radiology guidelines (19).

Statistical analysis was performed with SPSS software (version 20.0; IBM, Armonk, NY, USA). The chi-square statistic was used to evaluate patient and transplant characteristics. For outcomes that included five or fewer events, such as procedural success, a Fisher’s exact test was used. An independent samples t-test assuming unequal variances was used to compare means of continuous variables such as fluoroscopy time. Significance for all tests was set at P < 0.05.

Results

Demographics

A total of 190 recipients of liver transplants who underwent 306 transjugular liver biopsies were included in the study. Demographic information is summarized in Table 1. There were 116 men (61%) and 74 (39%) women, with 187 biopsies performed for men (61%) and 119 biopsies performed for women (39%). The most common reason for transplantation was cirrhosis due to viral hepatitis (n = 103), non-alcoholic steatohepatitis (n = 20), use of alcohol (n = 12), and autoimmune hepatitis (n = 10). The median age at biopsy was 57.7 years (age range = 12.5–80.6 years). The median age of patients at biopsy of bicaval and piggyback transplants was not statistically different (56.1 and 58.7 years, respectively; P = 0.29). Ninety-four of the transplants utilized bicaval anastomoses and 96 utilized piggyback anastomoses. A total of 252 biopsies were performed for 155 patients with whole livers versus 54 for 35 partial liver recipients. Among biopsies performed on partial liver transplants, 10 occurred in 9 deceased donor grafts, while 41 occurred in 26 living donor grafts.

Table 1.

Demographic data and comparative results based on hepatic vein anastomosis configuration.

Parameter	Bicaval (n = 94)	Piggyback (n = 96)	P value
Number of procedures	158	148
Age (years)	56.1 (19.1–80.6)	58.7 (18.4–76.3)	0.29*
Gender			0.17^†
Male	62 (66)	54 (56)
Female	32 (34)	42 (44)
Indication for transplant			0.82^‡
Viral hepatitis	49 (52)	54 (56)
Alcoholic cirrhosis	3 (3)	9 (9)
Cryptogenic cirrhosis	10 (11)	5 (5)
NASH	10 (11)	10 (10)
Autoimmune hepatitis	5 (5)	5 (5)
Primary biliary cirrhosis	4 (4)	5 (5)
Hepatocellular carcinoma	2 (2)	0 (0)
Drug toxicity	2 (2)	1 (1)
Other	10 (11)	6 (6)
Transplant type			<0.001^†
Whole liver	155 (98)	97 (66)
Partial liver (living donor)	0 (0)	44 (30)
Partial liver (deceased donor)	3 (2)	7 (5)
Time from transplantation to biopsy (months)	42.4 (0–354)	13.5 (0–214)	<0.001^†
Indication for biopsy			0.73^†
Elevated LFTs	99 (63)	101 (68)
Suspected rejection	18 (11)	9 (6)
Suspected viral hepatitis	18 (11)	21 (14)
Suspected fibrosis	23 (15)	17 (11)
INR	1.1 (0.9–2.0)	1.1 (0.9–2.1)	0.69*
>1.5	11 (7)	8 (5)
Platelets (×10⁹/L)	86 (24–154)	95 (36–186)	0.16*
<50	16 (10)	12 (8)
<100	98 (62)	82 (55)
Clinical portal hypertension	80 (51)	56 (38)	0.09^†
Ascites	79 (50)	54 (36)
Varices	35 (22)	23 (16)
Number of TJBx per transplant	1 (1–9)	1 (1–4)	0.52*
Number of needle passes per biopsy	3 (2–8)	3 (2–5)	0.55*
Procedural success			0.53^‡
Successful	154 (97)	142 (96)
Unsuccessful	4 (3)	6 (4)
Hepatic vein cannulation			0.03^‡
Successful	158 (100)	143 (97)
Unsuccessful	0 (0)	5 (3)
Number of portal tracts	10 (1–30)	11 (1–30)	0.07*
1–5	17 (10.1)	11 (7)
>6	124 (90)	121 (93)
Major hemorrhage	5 (3)	5 (3)	>0.99^†
Fluoroscopy time (min)	10.6 (2.4–24.5)	12.2 (2.4–61.6)	0.10*

Values are given as n (%) or median (range).

*T-test.

^†Chi-square test.

^‡Fisher’s exact test.

LFT, liver function test; NASH, non-alcoholic steatohepatitis; TJBx, transjugular biopsy.

All patients had thrombocytopenia (platelet count < 100,000/µL, n = 180), coagulopathy (INR > 1.5, n = 19), and/or ascites (n = 133), requiring a transjugular rather than percutaneous biopsy approach. The most common clinical indications for liver biopsy were elevated liver function tests (n = 200), suspected liver fibrosis (n = 40), recurrence of viral hepatitis (n = 39), and suspected rejection (n = 27). Clinical evidence for portal hypertension was present at the time of 136 (44%) biopsies, of which 115 (38%) and 58 (19%) procedures were performed in the setting of clinically evident ascites and documented varices. Coagulopathy was noted for 19 (6.2%) procedures and severe thrombocytopenia with platelet counts under 50 ×10⁹/L was present at the time of 28 (9.2%) procedures. A single biopsy procedure was performed for 117 (62%) patients, while 45 patients had two separate biopsy procedures (24%), and the remainder underwent up to nine separate biopsy procedures. Multiple biopsies were obtained in the same patient due to changes in patient clinical status over the eight-year study period, such as a new liver function test abnormality or evidence of worsening portal hypertension. A mean of 1.7 biopsies was performed per patient. The first post-transplant biopsy was performed on average 48.1 months after transplantation, and 12% of biopsies were performed within one month of transplantation. The mean time from transplantation to first post-transplant biopsy was 64.1 months for patients with bicaval anastomosis versus 31.1 months for patients with piggyback anastomosis (P < 0.001).

Procedural success

Of 306 procedures, 296 (96.7%) produced tissue samples adequate for histopathologic diagnosis and were deemed a procedural success. There were 10 procedural failures in 10 patients, four of which occurred in patients with bicaval anastomoses and six of which occurred in patients with piggyback anastomoses (P = 0.53). Procedural failures are summarized in Table 2. Five of the procedural failures were due to the inability to adequately position the stiff angled guiding cannula within the hepatic vein and the subsequent inability to obtain a tissue specimen. All of these failures occurred in patients with piggyback anastomoses (P = 0.03). In two of these procedures, the hepatic vein could not be catheterized, in one procedure the hepatic vein could not be cannulated with the angled outer sheath (Fig. 4), and in two procedures the stiff angled inner sheath could not be advanced into the hepatic vein through the outer angled sheath (Fig. 5). A femoral vein approach for intravascular liver biopsy was not attempted.

Table 2.

Summary of unsuccessful procedures.

Patient	Anastomosis	Transplant	Time from transplant (months)	Fluoroscopy time (minutes)	Mode of procedure failure*
1	Bicaval	Whole liver	53	n/a	1
2	Bicaval	Whole liver	4	n/a	1
3	Bicaval	Whole liver	35	n/a	2
4	Piggyback	Whole liver	89	9.6	2
5	Bicaval	Whole liver	3	n/a	2
6	Piggyback	Whole liver	35	n/a	3
7	Piggyback	Whole liver	7	42.4	3
8	Piggyback	Whole liver	7	20.8	3
9	Piggyback	Whole liver	6	61.6	3
10	Piggyback	Whole liver	68	14.6	3

*1 = insufficient sample (extrahepatic tissue); 2 = insufficient sample (low number and poor quality of portal tracts); 3 = inability to cannulate hepatic vein.

n/a, not available.

Fig. 4.

Transjugular hepatic venogram performed through a reverse curve angiographic catheter (Simmons 1, Cook, Inc.) due to unfavorable angle between the hepatic veins and IVC in a 59-year-old recipient of a liver transplant with a piggyback anastomosis. Neither the 10-Fr guiding sheath nor the stiffened biopsy cannula could be advanced into the hepatic vein due to the unfavorable angle between the hepatic vein and the IVC. IVC, inferior vena cava.

Fig. 5.

Transjugular hepatic venogram performed through a Cobra 2 catheter (a) and through a 10-Fr angled sheath (b) for a 65-year-old recipient of a liver transplant with a piggyback anastomosis. Due to the unfavorable angle, the stiffened biopsy cannula could not be advanced into the hepatic vein through the guiding sheath. Hepatic vein pressure gradient was 3 mmHg.

The remaining five procedural failures were due to inadequate core biopsy tissue sampling after successful vein cannulation. Four of these events occurred in patients with bicaval anastomosis and one in a patient with piggyback anastomosis (P = 0.37). Samples yielded extra-hepatic tissue for two of the patients with bicaval anastomoses (Fig. 6). The remaining three samples had low numbers of poor-quality portal tracts that prevented reaching a pathologic diagnosis.

Fig. 6.

Transjugular venogram showed no normal hepatic veins in a 68-year-old recipient of a liver transplant with a bicaval anastomosis. Linear spindly venous structures draining into the inferior vena cava were catheterized (a). At the time of the procedure, these structures were thought to represent abnormal hepatic veins. Stiffened biopsy cannula could be advanced into one of these veins and a biopsy was performed (b). Please note the use of the Rosen wire due to the short length of the available target vein. Pathology report described normal skeletal muscle, dense fibrous connective tissue, and vascular fibroadipose tissue. No liver tissue was identified. In retrospect, retroperitoneal or diaphragmatic draining veins likely catheterized.

Of the 10 patients with procedurally unsuccessful biopsies, five patients went on to have successful percutaneous biopsies, three went on to have successful repeat transjugular biopsy, and two deferred biopsies entirely. All three patients who went on to have a successful transjugular liver biopsy after the initial unsuccessful attempt had a bicaval anastomosis, and the procedural technique was identical to prior failed attempts. Those who went on to successfully repeat transjugular biopsy were included as a separate biopsy occurrence for statistical analysis.

The median number of needle passes performed during each procedure was 3 (range = 2–8), which did not significantly differ for patients with bicaval and piggyback anastomoses (Table 1). The number of portal tracts in tissue samples was recorded in 269 of the 306 pathology reports. The median number of portal tracts was 10 and 11 (P = 0.07) for transplants with bicaval and piggyback anastomoses, respectively. The percentage of biopsy samples with six or more complete portal tracts was 124 (90%) and 121 (93%) for transplants performed using bicaval and piggyback anastomoses, respectively (P = 0.40).

Safety

Major complications occurred following 10 of 306 (3.3%) biopsies in 10 separate patients. All complications involved hemorrhage, which was either documented by post-procedure imaging or clinically presumed (Table 3). Of note, all patients who developed a bleeding complication had platelet counts > 50,000/µL, and two of the patients had an elevated INR (1.6 and 1.7, respectively). The rest of the patients had INR levels 1–1.2.

Table 3.

Summary of major complications.

Patient	Anastomosis	Site of bleeding	Time from biopsy to bleeding detection (h)	Imaging modality to detect bleeding	Hemodynamic instability	Units of pRBCs transfused	Treatment
1	Bicaval	Right hepatic artery	>24	Angiography, ultrasound	Absent	2	Visceral angiography and coiling
2	Bicaval	Unknown	4–24	Ultrasound	Absent	2	Conservative management
3	Piggyback	Left capsule	<4	Ultrasound	Present	6	Laparotomy
4	Bicaval	Unknown	4–24	None	Absent	2	Conservative management
5	Bicaval	Unknown	4–24	Ultrasound	Absent	1	Conservative management
6	Bicaval	Unknown	4–24	Ultrasound	Absent	1	Conservative management
7	Piggyback	Subcapsular hematoma	<4	Ultrasound	Absent	3	Laparotomy
8	Piggyback	Left capsule	4–24	Ultrasound, Non-contrast CT	Present	2	Conservative management
9	Piggyback	Right intraparenchymal	>24	Ultrasound, CT angiography	Absent	1	Conservative management
10	Piggyback	Unknown	<4	None	Absent	2	Laparotomy

CT, computed tomography; pRBC, packed red blood cells.

Five major complications occurred in transplant recipients with a bicaval anastomosis and five occurred in transplant recipients with a piggyback anastomosis (P > 0.99). Three of the patients, all with piggyback anastomosis, underwent exploratory laparotomy. In two of these patients, there were no visible capsular injuries and no source of bleeding was identified. The third patient had developed a capsular laceration, with preoperative ultrasound and computed tomography (CT) imaging confirming the biopsy tract extending from the left hepatic vein to the capsule (Fig. 7). Eight of the 10 patients had suspected bleeding within the first 24 h and one patient developed melena nine days after the biopsy. Endoscopy performed 12 days after the biopsy showed bleeding from the ampulla of Vater, consistent with hemorrhage resulting in hemobilia. A hepatic angiogram performed on the same day showed a right hepatic artery pseudoaneurysm, which was embolized using fibered microcoils with subsequent resolution of hemorrhage (Fig. 8).

Fig. 7.

Axial computed tomography (a) with coronal reformat (b) performed on a patient with a left lobar liver transplant with signs of hemorrhage after transjugular liver biopsy. A linear hypodensity (a, straight black arrow) extends from the left hepatic vein (b, curved white arrow) to the posterior inferior liver capsule. At laparotomy a bleeding laceration was found in this location, presumably from the prior transjugular biopsy.

Fig. 8.

(a) Common hepatic angiogram performed in a patient who presented with melena and hemobilia nine days after transjugular liver biopsy. Angiogram showed a pseudoaneurysm (straight arrow) arising from a branch of the right hepatic artery. (b) Status after coil embolization (curved arrow) of the arterial supply to the pseudoaneurysm. Lo-flow Renegade microcatheter (Boston Scientific, Inc.) and fibered microcoils (3 × 2 mm Tornado; Cook, Inc.) were used for embolization. Subsequently the symptoms resolved.

In the remaining six patients with major bleeding, no additional intervention was performed, and presumed bleeding was self-limited. Patients with lobar transplants experienced a higher rate of major complication than patients with whole liver transplants, although this did not reach statistical significance (7.8% vs. 2.4%, P = 0.07). Patients with major complications trended towards having had recent liver transplants, with a mean transplant age of 15 months, compared to 49 months for patients without complications (P = 0.07). There were no reported deaths because of transjugular biopsy. None of the patients who developed major bleeding had evidence of de novo cirrhosis on pathology. Two of the 10 patients (20%) with a major complication had clinical evidence of portal hypertension, while the observed rate of portal hypertension was 44% for all 306 patients in the study. There was one recorded minor complication of bleeding at the jugular vein puncture site, which resolved with conservative measures.

Radiation dose

Fluoroscopy time data were available for 175 of 306 procedures, including 69 procedures performed for transplants with a bicaval anastomosis and 106 procedures for transplants with a piggyback anastomosis. Procedures performed for transplants with bicaval anastomoses involved an average of 12.1 min of fluoroscopy time versus 13.9 min for transplants with a piggyback anastomosis (P = 0.08). There was a trend toward longer fluoroscopy times for procedures that resulted in failure, averaging 29.8 min versus 12.7 min for successful procedures (P = 0.14). The total procedure time for each biopsy was not available.

Discussion

The procedural success rate of transjugular biopsies in this study was 96.7%, which is similar to previously reported rates of 95.5% in 269 procedures performed after liver transplantation by Miller et al. (16), and 96.8% reported in the review by Kalambokis et al. (10) comprising 7526 patients with native livers. Procedural failures due to the inability to position the stiff inner guiding sheath adequately within the hepatic vein were significantly more likely to occur for patients with piggyback anastomosis (P = 0.03). There was also a trend toward longer fluoroscopy times in all patients with piggyback anastomoses. Prior studies have shown that liver transplants anastomosed with the piggyback technique result in more acute angulation of the hepatic veins with the IFC. Together, these findings suggest cannulating a piggyback anastomosis may be more technically difficult (20 –22).

For technically challenging piggyback hepatic venous anastomosis cannulations, several alternative strategies may help improve success. One option would be to utilize a variety of catheter shapes, such as short angle-tip (Kumpe or Berenstein, Cook, Inc.) or a reverse curve catheter (Simmons 1 or 2, Sos, and/or Mikaelson, Cook, Inc.) in combination with a regular or a stiff guidewire. The selection of the catheter should be dictated by the angle between the suprahepatic IVC and the target hepatic vein as well as the IVC diameter at the anastomosis. Patulous suprahepatic IVC with a right or acute angle with the target hepatic vein may be successfully catheterized with a Cobra 2, Simmons, or a Mikaelson catheter. Alternatively, a narrow IVC could be approached with a short-angle Kumpe or Sos catheter, depending on the angle with the target hepatic vein. Of note, the angle between the IVC and the hepatic vein may become more favorable in deep inspiration, and this maneuver may facilitate all of the catheterization and catheter exchange steps. A Rosen 0.035-inch guide wire (Cook, Inc.) may be helpful for patients with a short hepatic vein, as this wire does not have a floppy tip and has an atraumatic 3-mm radius curve at the tip. If it is feasible to pass the 7-Fr occlusion balloon (Boston Scientific, Inc.) into the hepatic vein either over a super stiff or over a Rosen wire, inflation of the balloon within the hepatic vein may help anchor access within the hepatic vein and may facilitate passage of the 10-Fr. angle-tip guiding sheath. Manually adjusting the angle of the 14-gauge stiffening cannula may facilitate its passage into the target hepatic vein through the 10-Fr sheath. A transfemoral approach may also be considered (23,24).

The primary endpoint of procedural success was not statistically different for patients with piggyback and bicaval anastomoses. Procedural success depended on both successful hepatic vein cannulation and adequate liver tissue sampling. Of the five patients with inadequate tissue sampling, four had transplants with bicaval anastomosis and one had a transplant with a piggyback anastomosis (P = 0.38). This difference was enough to counter effects of increased difficulty cannulating the hepatic veins for patients with piggyback anastomoses. A commonly used metric for describing adequacy of tissue sampling is the number of complete portal tracts present in a sample, with the threshold for diagnosis of common liver pathology at least six portal tracts (18). In this respect, tissue sampling from grafts anastomosed with bicaval and piggyback technique was similar. Of note, the number of portal tracts obtained during the present study was higher than previously reported (10,25). These studies employed Menghini and Tru-Cut needles with a yield of 6.8 portal tracts on average. In the present cohort, a more modern core biopsy device (Cook, Inc.) was used exclusively. The higher average number of portal tracts (12.5 and 11.1 for bicaval and piggyback anastomoses, respectively) reported by the present study was likely due to the difference in the needle that was used.

The mean time from transplantation to biopsy was significantly longer for patients with bicaval anastomosis than for patients with piggyback anastomosis (P < 0.001). This difference may have reflected longer experience with creation of bicaval anastomoses at the study center. Alternatively, this difference may have been related to the tendency to use piggyback anastomoses for whole liver recipients who were unable to tolerate cross-clamping the inferior vena cava due to medical co-morbidities and/or tenuous hemodynamics. Thus, the earlier clinical need for a liver biopsy for patients with a piggyback anastomosis may have been related to patients’ underlying medical co-morbidities or smaller size of the transplanted liver (single lobe).

The rates of major complications were also nearly identical between the two groups, with an overall rate of 3.3%, similar to a reported 2.2% rate in a post-transplant population and to 2.5% rate in a series of 601 transjugular biopsies performed for patients with native livers (12,16). This highlights the need for careful post-biopsy follow-up of these patients. At the study center, outpatients undergoing transjugular liver biopsy are observed for a minimum of 4 h after the procedure. A hemoglobin level is drawn at the conclusion of the procedure and 3 h after the procedure. If there is suspicion for a bleeding complication, patients are admitted and further imaging is obtained either with contrast-enhanced CT angiography of the abdomen or abdominal ultrasound. In the present sample, there was a trend toward more major complications in patients with lobar grafts (4 of 54 procedures, 7.4%) compared to patients with whole liver grafts (6 of 252 procedures, 2.4%), although this was not statistically significant (P = 0.08). This supports results from prior work in which higher complication rates were noted in pediatric patients compared with adults, presumably due to decreased hepatic parenchymal volume (10). Other work has suggested that transjugular biopsy can be performed safely in such patients; however, special care should be taken to avoid capsular perforation (26). In order to minimize the risk of capsular perforation the central aspect of the liver should be biopsied and the arrow on the stiffened 7-Fr biopsy cannula can be utilized to ensure the biopsy sample is being taken from the desired portion of the liver. Typically, the cannula is torqued anteriorly from the right hepatic vein and posteriorly from the middle hepatic vein, though postoperative anatomy can be distorted, and it is good practice to evaluate any cross-sectional imaging which is available before biopsy to ensure the central aspect of the liver is being targeted.

Major complications happened more often in patients with recent liver transplants, although this did not reach statistical significance. There are several possible reasons for this trend. First, it is possible that recently anastomosed transplant veins are more susceptible to injury. For example, one patient in this series with the major complication of bleeding after biopsy who went to laparotomy had a blood clot near the recipient–donor hepatic vein anastomosis, suggesting possible anastomotic disruption during the biopsy procedure. Alternatively, recently transplanted patients may have more severe liver dysfunction, coagulopathy, and/or thrombocytopenia, increasing the risk of bleeding. Lastly, recently transplanted patients are more often inpatients when transjugular liver biopsy is performed. As such, otherwise clinically silent complications are more likely to be observed, and suspected complications are more likely to be presumed and acted upon. For example, no capsular injury was evident in two of the three patients who underwent laparotomy for presumed bleeding after biopsy. Waiting one month before performing a transjugular biopsy may be ideal in order to allow for the anastomosis to heal. However, earlier pathologic evaluation of the allograft may be required. Liver allografts as old as three days have been safely and successfully biopsied at our institution. Care needs to be taken to apply minimal torque on the allograft in the process of obtaining tissue samples in order to prevent disruption of the hepatic vein anastomosis.

Several limitations should be considered in the evaluation of the above results. As with any retrospective review, accuracy and completeness of data are dependent on accurate contemporaneous charting. In our review of the electronic medical record, there were no instances of non-bleeding complications associated with transjugular liver biopsy, such as carotid artery injury, pneumothorax, or arrhythmia. We found only one instance of a minor complication. This may in part result from incomplete documentation of minor events in the electronic medical record. Determining tissue specimen adequacy for pathologic diagnosis was also dependent on the clarity of pathology reports addressing the question being asked by clinicians. This question was most often to evaluate the cause of abnormal liver function tests in post-transplant patients. Transplant surgical anatomy was categorized into two groups: bicaval and piggyback anastomoses. The piggyback group included whole and partial deceased donor livers with piggyback anastomosis and living donor transplants. While this grouping makes intuitive sense from the perspective of postoperative anatomy observed at hepatic venography, it may not capture the full spectrum of anastomotic configurations. For example, Kaufman et al. (13) proposed three venous anastomotic categories: bicaval; piggyback; and “side to side.” Another consideration is that while we focused on the surgical anastomotic technique—because this information is readily available to the interventional radiologist before starting the procedure—a more direct determinant of the technical success rate may be the angle of the right hepatic vein and the IVC (27). In our series, alternative techniques for technically challenging cases, such as transcaval biopsies or femoral access, were not attempted when the hepatic veins were not successfully cannulated by standard methods (12,28). All the procedures were performed using the Liver Access and Biopsy Set (Cook Medical, Inc.), which limited generalizability of our findings for centers who use other types of access sets.

With respect to the statistical analysis, the small number of observed procedural failures precluded use of multivariable logistic regression and generalized linear regression with clustering statistical tests (29). This introduced the possibility of interdependence in our dataset, which was not accounted for in standard statistical models (30).

In conclusion, transjugular liver biopsy is a safe procedure that commonly provides adequate liver tissue for histopathologic diagnosis for liver transplant recipients with both bicaval and piggyback hepatic vein anastomoses. While cannulation of hepatic veins after a piggyback anastomosis may be more difficult, failure to obtain adequate tissue is rare. The type of anastomosis does not significantly affect risk of major hemorrhage, although bleeding may be more common for split graft recipients and in the setting of recent transplantation.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Nicholas Fidelman

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