Keywords
TIPS - varices - hemorrhage - portal hypertension - interventional radiology
Emergent transjugular intrahepatic portosystemic shunt (TIPS) creation is most commonly
employed in the setting of acute variceal hemorrhage (VH), a dreaded complication
of portal hypertension in patients with liver cirrhosis. Given a propensity for decompensation,
these patients often require a multidisciplinary, multimodal approach involving prompt
diagnosis, pharmacologic therapy, and endoscopic intervention.[1]
[2]
[3]
[4] While successful in the majority of cases, failure to medically control initial
bleeding can prompt interventional radiology (IR) consultation for emergent portal
decompression via TIPS creation. This article discusses TIPS creation in emergent,
acute VH, reviewing the natural history of gastroesophageal varices (GEVs), presentation
and diagnosis of acute VH, pharmacologic therapy, endoscopic approaches, patient selection
and risk stratification for TIPS, technical considerations for TIPS creation, adjunctive
embolotherapy, and the role of salvage TIPS versus early TIPS in acute VH.
Gastroesophageal Varices
Portal hypertensive hepatic venous pressure gradients (HPVGs)—defined as pressure
gradients ≥ 10 mm Hg—result in GEV formation via a dynamic, multifactorial process.[3]
[5] GEVs progress with worsening liver cirrhosis, and are categorized as “small” (<
5 mm), “medium” (based on tortuous morphology and occupation of less than one-third
of the esophageal lumen), and “large” (> 5 mm).[3]
[6]
[7]
[8] Classically, EVs are reported in 52% of endoscopically screened patients, and increase
in prevalence with disease severity, conservatively ranging from 43% in patients with
Child-Pugh class A disease to 72% of patients with Child-Pugh class B/C disease.[9] EVs are reported to have an annual formation incidence of 7 to 9%[10]
[11]
[12] and an annual progression rate of 10 to 15%.[13]
[14]
[15] Given these rates, approximately 90% of cirrhotic patients have EVs at 10 years.[16] In contrast, GVs are less prevalent, and are reported in 5 to 33% of patients with
liver cirrhosis.[17]
[18] Today, EVs and GVs are delineated as unique anatomic entities with varying physiologic
behavior. EVs exist at higher pressures than GV: 16 to 24 mm Hg vs. 11 to 18 mm Hg.[13]
[14] While problematic EVs are historically located within the lower 5 cm of the distal
esophagus,[19]
[20] GVs exist at locations which are demarcated by the Sarin classification system.[17] In this classification scheme, gastroesophageal varices type 1 (GEV1) occur at the
lesser curvature of the stomach, gastroesophageal varices type 2 (GEV2) at the greater
curvature of the stomach, and isolated gastric varices type 1 (IGV1) at the fundal
region. Ectopic isolated gastric varices type 2 (IGV2) are rarely encountered.
EV hemorrhage is generally thought to account for up to 70% of upper gastrointestinal
(GI) bleeding in patients with liver cirrhosis,[1]
[21] and occurs at variable rates. Small EV hemorrhage is known to occur at 5% yearly,
versus 15% annually for medium and large EV hemorrhage.[22] Comparatively, GV hemorrhage occurs 50% less frequently than EV hemorrhage, and
is attributed to between 10 and 30% of all VH.[17] Although less frequent, GV hemorrhage rates are reported to occur at 16% at 1 year,
36% at 3 years, and 44% at 5 years, often with high transfusion requirements due to
severity of bleeding.[17]
[18] Data show that GV hemorrhage occurs at lower portosystemic gradients (PSGs)—approximating
16 to 20 mm Hg—when compared with EV hemorrhage (21–23 mm Hg), with 10% of GV hemorrhage
and 2% of EV hemorrhage occurring at PSGs below 12 mm Hg.[23]
[24]
Prevention of First Variceal Hemorrhage
Prevention of First Variceal Hemorrhage
Given the high prevalence of varices in liver cirrhosis, patients with this condition
undergo screening endoscopy at the time of liver disease diagnosis, with follow-up
surveillance every 2 to 3 years, or every 1 to 2 years if small varices are present.[3]
[25]
[26] Additionally, endoscopy is recommended upon declaration of cirrhotic decompensation
and yearly thereafter.[3]
[7]
[26] Ideally, this strategy allows for prevention of first VH.
Prevention of VH is best understood in the setting of EV. Treatment hinges on maintaining
a protective HPVG ≤ 12 mm Hg,[3]
[27] with definitive endoscopic treatment of varices. Patients with medium and large
EVs, and those with decompensated cirrhosis or stigmata of bleeding—such as red wale
signs—are often treated with nonselective β-blockade (using propranolol, nadolol,
or carvedilol) or endoscopic variceal ligation (EVL) to potentially prevent variceal
progression and hemorrhage.[3]
[25]
[28]
[29] Combination therapy is usually not performed.[3]
Comparatively, prevention of GV hemorrhage is less understood. A randomized controlled
trial (RCT) examined the use of sclerosant glue compared with nonselective β-blockade
or observation and demonstrated similar survival between β-blockade and sclerosant
utilization.[3]
[30] Prospective evaluation of variceal obliteration is yet to be adequately performed
in this setting.[31]
Diagnosis of Variceal Hemorrhage
Diagnosis of Variceal Hemorrhage
Patients with acute VH often present with hematemesis or melena, and variable states
of hemodynamic stability. Assessment begins by obtaining a detailed history from the
patient or family, complemented by thorough chart and imaging review, which will often
yield a history of liver cirrhosis, portal hypertension, and/or GEVs. Baseline laboratory
assessment includes a complete blood count, comprehensive metabolic panel, and a basic
coagulation panel.
Differentiation between acute VH and other sources of upper GI bleeding in the cirrhotic
patient is an important consideration, as this population experiences nontrivial rates
of peptic ulcer disease.[32]
[33] As the interventional approach to arterial and variceal bleeding sources differs
substantially, clear delineation of the hemorrhage source is compulsory ([Fig. 1]). While endoscopy serves as the primary means to diagnose bleeding sources, multiphase
computed tomography angiography (CTA) may serve as an adjunctive modality to determine
whether there is active arterial hemorrhage, determine a source, and provide a potential
roadmap for intervention.[34] Additionally, a properly performed venous phase can help identify ectopic (e.g.,
small bowel) varices that cannot be identified with conventional endoscopy. Intravenous
proton pump inhibitors (PPIs) are often initiated in the setting of upper GI bleeding,
and their use remains controversial in cirrhotic patients.[1] PPIs may be discontinued upon confirmation of VH[4] given an association with spontaneous bacterial peritonitis.[35]
Fig. 1 TIPS in the setting of elevated MELD score. A 49-year-old woman with hepatitis C
virus liver cirrhosis referred to IR for emergent TIPS in the setting of massive EV
bleeding and disseminated intravascular coagulation. At the time of referral, patient
failed endoscopic treatment and was in critical condition with calculated MELD score
of 40. TIPS created uneventfully (arrow), and laboratory and clinical findings following procedure supported bleeding cessation.
Nonetheless, patient's condition did not improve, a do-not resuscitate status was
assigned, and she died due to multiorgan failure 2 days post-TIPS. Though TIPS may
be applied in acutely bleeding patients with high MELD scores, likelihood of survival
is extremely poor. Given poor anticipated clinical outcomes, open discussion that
conveys anticipated course to patient and family is critical in clinical decision-making
process.
Pharmacotherapy, Endoscopy, and Bridge to Salvage TIPS
Pharmacotherapy, Endoscopy, and Bridge to Salvage TIPS
Upon confirmation of acute VH, treatment aims to achieve hemostasis, prevent early
rebleeding, and minimize 6-week mortality.[3]
[25]
[36] Patients experiencing acute VH demand high acuity of care, often requiring monitoring
within an intensive care unit equipped with skilled nursing staff and a multidisciplinary
team of critical care specialists, hepatologists, GI endoscopists, interventional
radiologists (IRs), and surgeons.[26]
Initial management involves airway control, especially in the setting of hematemesis
and hepatic encephalopathy (HE). Prophylactic intubation is controversial[26] and has been associated with higher risk of aspiration pneumonia.[37] Thus, the decision to intubate is made on a case-by-case basis.
Volume resuscitation is challenging, and conservative transfusion protocols are utilized.
A mean arterial pressure goal of approximately 65 mm Hg—extrapolated from data regarding
the management of septic shock and trauma[38]
[39]
[40]
[41]—is usually pursued.[1] Hypovolemia at presentation may temper VH by decreasing portal pressure, while aggressive
resuscitation can aggravate VH or promote rebleeding by elevating portal pressure.[4]
[42]
[43] A RCT demonstrated improved survival in patients with Child-Pugh class A and B disease,
with decreased overall rebleeding in all Child-Pugh class A, B, and C patients, when
transfusion occurred below hemoglobin of 7 g/dL with a posttransfusion target of 7
to 9 g/dL.[4]
[44] Current treatment recommendations incorporate these parameters.[3]
Pharmacologic therapy to achieve hemostasis emphasizes splanchnic vasoconstriction
in lieu of correction of coagulopathy. No benefit has been shown when factor VII is
administered to correct prothrombin time.[4]
[45]
[46] Moreover, no compelling data are available regarding correction of thrombocytopenia
or use of desmopressin.[3]
[4]
[47] Current pharmacologic options to achieve hemostasis include intravenous splanchnic
vasoconstriction with octreotide, somatostatin, or terlipressin, administered for
up to 3 to 5 days.[3]
[25]
[48] This recommendation is supported by a meta-analysis of RCTs that demonstrated improved
hemostasis, decreased blood transfusions, and lower 7-day mortality with utilization
of splanchnic vasoconstriction.[3]
[49]
Antibiotic prophylaxis is initiated, given high risk for cirrhotic patients with upper
GI bleeding to develop gram-negative bacterial infections,[1]
[50]
[51]
[52] which are postulated to occur due to translocation of enteral flora. RCTs and meta-analyses
exploring antibiotic prophylaxis have demonstrated decreased infection rates, rebleeding,
and mortality.[3]
[50]
[52] Due to prevalent quinolone resistance, 1 g ceftriaxone is usually administered every
24 hours for 7 days.[3]
[25]
[53]
Prompt endoscopy (within 12 hours) is recommended,[3]
[25] as patients experiencing VH may rapidly decompensate. Endoscopy allows for definitive
treatment of bleeding varices by EVL or endoscopic injection sclerotherapy (EIS).[26]
[31]
[54]
[55] Data show increased in-hospital mortality when endoscopy is delayed by more than
15 hours in hemodynamically stable patients,[4]
[56] and that endoscopy within 12 hours is associated with lower rates of rebleeding
and mortality.[57] Timing remains debated, as others report no overall impact on mortality with delayed
endoscopy in stable patients.[56]
[58]
[59]
While EV hemorrhage is typically treated by combination EVL and splanchnic vasoconstriction,[3]
[4]
[25]
[48] GV hemorrhage is often difficult to ameliorate by EVL secondary to anatomic considerations,
and suboptimal EVL can lead to ulceration and subsequent bleeding.[31]
[60] While a meta-analysis has shown that cyanoacrylate glue is associated with lower
rebleeding rates in GVs, EVL and EIS have comparable rates of hemostasis.[3]
[61]
Despite attempts to optimize combined pharmacotherapy and endoscopic treatment, acute
VH is refractory in approximately 10 to 20% of patients,[16]
[62] and temporizing measures must be considered prior to rapid portal decompression
via TIPS creation. Today, bridging measures such as self-expanding metal stent (SEMS)
deployment or 24-hour balloon tamponade (using Sengstaken-Blakemore, Linton-Nachlas,
or Minnesota tubes) are utilized. Overall, utilization of balloon tamponade correlates
with severity of bleeding and is successful in up to 80% of patients, although its
use in VH is associated with increased adverse events and mortality rates of 20%.[3]
[7]
[ 63]
[64] Comparatively, SEMS can be left in place for up to 7 days[4] and have demonstrated both better hemostasis and less adverse events,[3]
[65]
[66]
[67] although stent migration remains a worrisome complication.[68]
TIPS Indications
Current indications for TIPS creation in VH are summarized by the American Association
for the Study of Liver Diseases (AASLD)[3]:
-
Rescue therapy for acute VH which is refractory to pharmacologic and endoscopic treatment.
-
Recurrent VH despite optimization of pharmacology and endoscopic treatment.
-
Emerging indication for early (within 24–72 hours) TIPS creation in acute VH.
TIPS is not pursued for prevention of VH in nonbleeding varices, prevention of rebleeding
in patients who have experienced only one episode of EV hemorrhage, prevention of
hemorrhage from gastric antral vascular ectasia, or portal hypertensive gastropathy.[69]
[70]
While no absolute contraindications exist, relative contraindications for TIPS creation
are presented by the Society for Interventional Radiology.[71] Briefly, relative contraindications include heart failure or major valvular insufficiency,
elevated left or right heart pressures, rapidly progressive liver failure, severe
or uncontrolled HE, uncontrolled systemic infection, sepsis, unrelieved biliary obstruction,
polycystic liver disease, extensive primary or metastatic hepatic malignancy, and
severe uncontrolled coagulopathy.[71]
Patient Selection and Risk Stratification
Patient Selection and Risk Stratification
Patient selection is a challenging endeavor for the IR, as individuals experiencing
acute VH often have decompensated cirrhosis. It has long been known that the markedly
elevated portal pressures in decompensated cirrhosis contribute to morbidity and mortality
in VH. HPVG measurements ≥ 20 mm Hg are associated with failure to achieve hemostasis
and early rebleeding.[72]
[73] Moreover, HPVGs ≥ 16 mm Hg have also been associated with mortality[22] and elevated serum bilirubin has been reported to increase risk of mortality with
each 1 mg/dL increase above a threshold of 3.0 mg/dL.[74] These and other objective surrogate markers guide decision making.
Currently, the Model for End-Stage Liver Disease (MELD) score is the predominant system
utilized for objective risk stratification and patient selection for TIPS creation.[75] MELD utilizes serum total bilirubin, international normalized ratio (INR), and serum
creatinine as surrogate markers to assess liver function and has classically and contemporaneously
(with and without modification) demonstrated efficacy in predicting mortality.[76]
[77]
[78]
[79]
[80]
[81]
[82] Moderately elevated short-term mortality rates are evident in patients with MELD
scores exceeding 18, and markedly elevated short-term mortality rates occur above
the MELD threshold of 25 ([Fig. 2]).[83] Moreover, the MELD score has successfully been extrapolated in the emergent setting
to predict 90-day mortality with high accuracy (area under the receiver operating
characteristics: 0.842, 95% confidence interval [CI]: 0.755–0.928).[84] Similarly, Conejo et al examined Child-Pugh and MELD scores in patients with decompensated
cirrhosis experiencing acute VH, and reported that MELD scores exceeding 19 and Child-Pugh
class C disease confer high risk of death.[85]
Fig. 2 TIPS for presumed variceal bleeding with subsequent discovery of arterial bleeding
source. A 73-year-old man with alcoholic cirrhosis and acute VH transferred from outside
hospital for possible TIPS creation. Upper endoscopy performed 1 week prior revealed
bleeding EVs. Upon transfer, recurrent EV bleeding presumed, though active bleeding
source not established via repeat endoscopy. While TIPS was successfully created (a; arrow), patient continued to have hematochezia and decreasing hemoglobin levels. Repeat
upper endoscopy revealed bleeding duodenal ulcer. Arteriography confirmed active hemorrhage
from gastroduodenal artery (b; arrow), and bleeding cessation achieved after coil embolization (c; arrow). Appropriate preprocedural diagnosis and workup is critical in establishing source
of upper GI bleeding prior to therapy prescription, to recommend most suitable management
approach.
Even with high predictive value, criteria such as MELD score cannot be solely utilized
for patient selection. Despite poor prognosis in severely decompensated liver disease,
emergent portal decompression by TIPS creation is considered a potentially lifesaving
measure in refractory acute VH. Thus, patients should be selected on a case-by-case
basis. Critical conversations, including a potential need for liver transplantation,
are necessary between the patient (or family), referring service, and operating IR.
Minor complication rates (up to 4%) should be discussed, along with major complication
rates (up to 3%), and relevant potential risks including persistent VH (i.e., therapeutic
failure), hepatic infarction, severe or life-altering HE, and death.[71] Additionally, if GV hemorrhage is suspected, there is potential to offer an alternative
endovascular approach that obliterates bleeding GVs with or without TIPS creation.[86]
TIPS Technical Considerations and Postprocedural Care
TIPS Technical Considerations and Postprocedural Care
Since the conceptualization of TIPS over 40 years ago, technical considerations for
shunt creation have been described thoroughly and revisited in detail.[87]
[88]
[89] TIPS creation commonly involves the formation of a tract between the right hepatic
vein and right portal vein. This is most commonly achieved by selecting the right
hepatic vein and utilizing wedged hepatic venography to identify the right portal
vein. A needle is fluoroscopically targeted toward a right portal vein branch. The
PSG may be calculated once successful portal venous access has been achieved. Contemporary
TIPS are generated by deployment of a stent graft (Viatorr; W.L. Gore, Flagstaff,
AZ) for shunt creation. Bare metal stents are rarely used in modern TIPS procedures,
given reduced overall patency and association with increased rebleeding rates and
decreased survival[87]
[90]
[91]
[92]
[93]
[94]; nonetheless, there may be specific clinical scenarios that merit consideration
of bare metal stent TIPS creation ([Fig. 3]). After stent-graft deployment, the shunt tract is dilated incrementally with an
8- to 10-mm balloon to a target PSG ≤ 12 mm Hg.[89] Additional splenic and portal venography can be performed to detect varices, which
may serve as targets for embolization, most commonly the left gastric (coronary) vein,
posterior gastric vein, and short gastric vein.[89]
[95] Moreover, if GVs are present, the operator may choose to obliterate varices at the
time of TIPS creation or pursue staged obliteration at a later date.[86] Importantly, balloon tamponade devices need to be deflated after shunt creation
to ensure variceal decompression and to allow catheter access to varices if embolization
or obliteration is to be pursued. Another important consideration when treating acute
VH is preprocedural correction of coagulopathy,[96] which is often not pursued in the cirrhotic patient prior to salvage therapy.
Fig. 3 Bare metal stent TIPS in the setting of bacteremia. A 63-year-old man transferred
for management of actively bleeding EVs after unsuccessful banding. Patient presented
with fever, leukocytosis, and computed tomography findings of colitis. There was clinical
concern for bacteremia, though culture results were pending. TIPS was created using
bare metal stent (a; arrow) to avoid potential risk of stent-graft colonization, with plan to revise stent-graft
TIPS when blood cultures confirmed to be sterile. After TIPS, bleeding stopped, and
patient returned 5 days later for successful shunt relining using PTFE-covered stent
graft (b; arrow). Infection of TIPS stent grafts—termed endotipsitis—is an infrequent but serious
complication associated with high mortality rates. As such, bacteremia or uncontrolled
sepsis is considered a relative contraindication for TIPS creation. In such scenarios,
bare metal stent may offer lower risk of colonization, given absence of covering graft
material.
In the post-TIPS period, the acute VH patient is generally monitored in the intensive
care unit to monitor for hemodynamic stability, resolution of hemorrhage, TIPS-related
adverse events, and neurological signs of HE.[86] Alongside monitoring nasogastric tube output, serial hemoglobin and hematocrit values
may be obtained to monitor cessation of VH. A follow-up liver panel and coagulation
panel are also obtained the day after the procedure to assess hepatic function. TIPS
patency may be monitored with serial Doppler ultrasound at 1, 3, and 6 months postprocedure.
TIPS Creation for Initial Control of VH
TIPS Creation for Initial Control of VH
TIPS creation is nearly always technically feasible and is a bona fide treatment for
initial control of acute VH,[75]
[97] as historical datasets report rates of hemostasis between 89 and 100%,[98]
[99]
[100]
[101]
[102]
[103]
[104]
[105]
[106]
[107]
[108]
[109] largely in EV hemorrhage. However, historical cohorts have demonstrated variable
rebleeding rates,[97] which may be inflated due to early widespread utilization of uncovered bare metal
stents prior to the advent of the bile impermeable polytetrafluoroethylene (PTFE)
stent grafts, which prevent bile-mediated thrombosis and TIPS dysfunction.[110] For instance, a recent retrospective cohort demonstrated significantly lower rebleeding
rates (14 vs. 37%, odds ratio [OR] = 0.259; p < 0.001) and need for shunt revision when comparing PTFE TIPS stent grafts with bare
metal stents.[93]
Historically, studies have reported variable short-term mortality rates for salvage
TIPS, ranging between 19 and 60%.[97] Tenuous outcomes continue to be reported for salvage TIPS in hemodynamically unstable
patients. Active hemorrhage at the time of TIPS creation has been associated with
a 2.9-fold greater odds of death.[74]
[111] A recent retrospective analysis reported approximately 34% mortality at 30 days
in patients with hemorrhagic shock undergoing salvage TIPS, in addition to overall
unfavorable clinical outcome.[112]
While studies examining TIPS in acute VH are variable due to inclusion criteria and
methodology, recent studies demonstrate similar outcomes for rebleeding and overall
survival. Gaba et al reported 1-month rebleeding rates less than 10% with rebleeding
rates of 22% at 1 year and nearly 30% at 2 years, and survival rates of 80, 69, and
65% at 30 days, 1-year, and 2 years, respectively.[113] Zhu et al recently reported similar findings, including rebleeding rates of 11,
17, and 20% at 6 weeks, 1 year, and 2 years, respectively.[114] Transplant-free survival was reported to be 88, 82, and 74% at 6 weeks, 1 year,
and 2 years, respectively.[114] Longer term survival data remain sparse. Notably, Sanyal et al reported 46% survival
at a median follow-up period of 920 days after salvage TIPS, while Azoulay et al reported
1-year survival of 51 and 40% at 3 and 5 years[98]
[105]; however, these datasets preceded the era of PTFE-covered stent grafts.
Additionally, comparison between emergent TIPS and creation of a surgical portosystemic
shunt (SPSS) remains debated. A recent systematic review demonstrated low confidence
when assessing RCTs that demonstrated higher rates of all-cause mortality (RR: 0.61,
95% CI: 0.42–0.90), rebleeding (RR: 0.19, 95% CI: 0.08–0.49), reintervention (RR:
0.13, 95% CI: 0.06–0.28), and shunt occlusion (RR: 0.14, 95% CI: 0.040–0.51) at 5
years with TIPS versus SPSS. Given the high numbers of bare metal stents utilized
in available datasets,[115]
[116]
[117]
[118] prospective data exclusively utilizing PTFE-covered TIPS are necessary.
TIPS Creation for GV Hemorrhage
TIPS Creation for GV Hemorrhage
TIPS for GV hemorrhage requires more data. TIPS has been reported to achieve bleeding
control in 90% of bleeding GVs[107]
[119] and, in a RCT, demonstrated significantly lower rebleeding from GV hemorrhage when
compared with endoscopic glue obliteration at a median follow-up of 33 months.[120] However, recent data suggest that TIPS may not be the optimal modality for addressing
GV hemorrhage, which bleed at lower pressures with recent data demonstrating a rebleeding
rate of 27 and 15% mortality at 90 days.[121] Therefore, patients presenting with GV hemorrhage may be considered for concurrent
obliteration in addition to TIPS.[86]
Early TIPS Creation for Acute VH
Early TIPS Creation for Acute VH
Early nonsalvage TIPS creation (usually within 72 hours) is an emerging indication
in VH with promising results. Early TIPS supplements initiated pharmacologic and endoscopic
interventions, and is theorized to mitigate background elevated portal pressure and
prevent rebleeding.[122] Initially, a RCT with 116 consecutive patients utilized uncovered stents in early
VH (24 hours), and demonstrated that patients with HPVG ≥ 20 mm Hg had significantly
less treatment failure (12 vs. 50%) and transfusion requirements when compared with
those not undergoing TIPS.[123] This study also reported significantly lower in-hospital and 11-year mortality (11
and 31%, respectively).[123] Subsequently, a RCT of patients with Child-Pugh B/C VH showed improved rates of
bleeding control (97 vs. 50%), 6-week survival (97 vs. 67%), and 1-year actuarial
survival (86 vs. 61%) with a PTFE-covered TIPS versus pharmacologic and endoscopic
therapy.[124] A subsequent retrospective review comparing TIPS versus combination pharmacotherapy
and endoscopy in the same center demonstrated similar findings, as the TIPS group
experienced significantly lower rates of failure to control bleeding or rebleeding
(93 vs. 50%) and improved 1-year actuarial survival (86 vs. 70%).[125] Another prospective study aimed at external validation of initial results, and demonstrated
significantly lower 1-year probability for rebleeding with early TIPS creation in
a similar patient cohort (97 vs. 51%; p < 0.001), but reported no difference in actuarial survival.[126]
Recent data are also available. A multicenter observational study comparing early
TIPS and combination pharmacotherapy and endoscopy in 631 patients demonstrated significantly
improved survival at 1 year when comparing early TIPS to combination pharmacotherapy
and endoscopy in patients with Child-Pugh C disease along with reduced treatment failure
(which incorporated rebleeding).[60] Additionally, a recent RCT examining early covered TIPS with pharmacologic therapy
and endoscopy examined transplant-free survival as an endpoint and demonstrated significantly
improved transplant-free survival at 6 weeks and 1 year in patients who received early
TIPS.[127]
Several meta-analyses have also been performed. An analysis from 2015 evaluated randomized
and nonrandomized data in early TIPS creation, reporting fewer deaths (OR: 0.38, 95%
CI = 0.17–0.83; p = 0.02) and lower rates of rebleeding within 1 year in patients with Child-Pugh B
(OR: 0.08, 95% CI: 0.04–0.17; p < 0.001) and Child-Pugh C (OR = 0.05, 95% CI = 0.02–0.15; p < 0.001) disease.[128] A subsequent meta-analysis echoed these findings, reporting significantly decreased
inpatient mortality (RR = 0.87) and rebleeding (RR = 0.56).[129] Notably, early TIPS did not demonstrate increased HE in these studies, which is
an important consideration for patients, families, consulting physicians, and operators.
Additionally, a 10-year retrospective inpatient dataset of 142,539 patients with decompensated
cirrhosis and EV hemorrhage demonstrated significantly decreased rebleeding (RR = 0.56)
and inpatient mortality (RR = 0.87) with early TIPS when compared with no TIPS.[130] Significantly less inpatient rebleeding, death, and cost were observed as well.[130] Additional analysis compared early TIPS versus salvage TIPS, yielding significantly
less inpatient rebleeding, death, length of stay, and cost for the early TIPS group.[130] These latter results may reflect the dire clinical circumstances encountered when
salvage TIPS is considered.
TIPS Creation with Adjunctive Embolotherapy
TIPS Creation with Adjunctive Embolotherapy
Adjunctive embolotherapy of varices is a protective measure used alongside TIPS creation,
and is theorized to not only result in variceal occlusion, but may also serve to maintain
TIPS patency by eliminating competing variceal shunts which could contribute to TIPS
dysfunction and promote subsequent GEV formation and VH.[97]
[131]
[132] The embolization procedure may be staged prior to or following TIPS creation.[86] Post-TIPS variceal embolization allows the operator to view optimized filling of
the newly created TIPS and its impact on variceal filling. Alternatively, preprocedural
embolotherapy has the benefit of improved variceal filling to guide targeting. Moreover,
embolotherapy performed before TIPS creation avoids an avenue for embolic agent migration
and nontarget embolization.
Although controversial, adjunctive embolotherapy has been utilized in up to 48% of
patients[97]
[131] and has largely favorable results considering prospective and retrospective data.[86] Prospective studies have shown significant reductions in rebleeding rates with adjunctive
embolotherapy when compared with TIPS alone.[132]
[133]
[134] Retrospective data are mixed, with a majority of studies with significant reductions
in rates of rebleeding when adjunctive embolotherapy is utilized.[135]
[136] Other retrospective data demonstrate lower, although nonsignificant, rates of rebleeding
between combined treatment and TIPS alone.[88]
[137]
[138] Moreover, a meta-analysis comparing combined TIPS and adjunctive embolotherapy versus
TIPS alone reported that combined therapy significantly reduces rebleeding and improves
TIPS patency at 6 months.[139] A recent retrospective study exploring adjunctive embolotherapy reported nearly
6% rebleeding rate at a median follow-up time of 26 months with approximately 1 and
3% rebleeding rates at 1 and 2 years.[140]
Conclusion
Patients with decompensated liver cirrhosis and acute VH require multifaceted, multidisciplinary
treatment. Emergent TIPS creation successfully ameliorates acute VH when standard
medical and endoscopic management are unsuccessful, and recent data demonstrate a
promising role for early, nonsalvage TIPS creation in acute VH. Patient selection
and risk stratification for this potentially life-saving procedure remains challenging
and continues to be determined on a case-by-case basis. Decision making can be aided
by objective measures such as MELD score along with anatomic considerations such as
the presence of bleeding GVs which could benefit from obliteration or combined TIPS
approaches.
