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382
Table 34.2 The main outcomes of endoscopic therapy ± pharmacological therapy versus TIPS in
the management of variceal hemorrhage
Study (year)
Study type
( quality of
evidence)
Patients
(C vs. T)
Treatment
failure (C vs.
T)
Hepatic
encephalopathy
(C vs. T)
Mortality (C
vs. T)
Cabrera (1996) RCT
(moderate)
32 vs. 31 52 % vs. 23 % 13 % vs. 33 % 18 % vs. 7 %
p < 0.02 p < 0.05 p=n.s
Cello (1997) RCT
(moderate)
25 vs. 24 48 % vs. 13 % 44 % vs 50 % n.s
p = 0.012 p = 0.2
Jalan (1997) RCT
(strong)
27 vs. 31 52 % vs. 10 % 11 % vs 16 % n.s
p < 0.0006 p=n.s
Rossle (1997) RCT
(moderate)
65 vs. 61 52 % vs. 21 % 18 % vs. 36 % 11 % vs.
10 %
p = 0.001 p = 0.011 p=n.s
Sanyal (1997) RCT
(moderate)
39 vs. 41 26 % vs. 24 % 13 % vs. 29 % 18 % vs.
29 %
p = 0.2 p = 0.01 p = 0.02
Sauer (1997) RCT
(moderate)
41 vs. 42 57 % vs. 23 % 13 % vs. 29 % 33 % vs.
31 %
p = 0.0001 p = 0.041 p = 0.62
Merli (1998) RCT
(moderate)
43 vs. 38 51 % vs. 24 % 26 % vs. 55 % 19 % vs.
24 %
p = 0.11 p = 0.006 p = 0.50
GarciaVillarreal
(1999)
RCT
(moderate)
24 vs. 22 50 % vs. 9 % 25 % vs. 23 % 33 % vs.
15 %
p < 0.001 p=n.s p < 0.05
Narahara
(2001)
RCT
(moderate)
40 vs. 38 32 % vs. 18 % 15 % vs. 32 % 18 % vs.
29 %
p > 0.05 p < 0.05 p = 0.35
PomierLayrargues
(2001)
RCT
(strong)
39 vs. 41 66 % vs. 18 % 44 % vs. 47 % 47 % vs.
43 %
p < 0.001 p=n.s p=n.s
Gulberg (2002) RCT
(moderate)
26 vs. 28 16 % vs. 17 % 4 % vs. 7 % 16 % vs. 8 %
p=n.s p=n.s p=n.s
Sauer (2002) RCT
(strong)
42 vs. 43 30 % vs. 19 % 20 % vs. 40 % 18 % vs.
24 %
p = 0.32 p < 0.05 p=n.s
Monescillo
(2004)
RCT
(moderate)
26 vs. 26 50 % vs. 12 % 35 % vs. 31 % 65 % vs.
31 %
p = 0.0001 p=n.s p = 0.01
Garcia-Pagan
(2010)
RCT
(strong)
31 vs. 32 50 % vs. 3 % 39 % vs. 25 % 39 % vs.
14 %
p < 0.001 p=n.s p = 0.001
C control group ( endoscopic treatment ± pharmacological therapy), T treatment groups ( TIPS ),
RCT randomized control trial, n.s not shown
A. Teriaky and A. Aronsohn
383
decreased the incidence of recurrent variceal bleeding (odds ratio (OR) = 0.32, 95 %
confi dence interval (CI) (0.24–0.43), p < 0.00001), increased the rate of encephalopathy (OR = 2.21, 95 % CI (1.61–3.03), p < 0.00001), decreased deaths due to
rebleeding (OR = 0.35, 95 % CI (0.18–0.67), p = 0.002) but did not cause an overall
mortality benefi t (OR = 1.17, 95 % CI (0.85–1.61), p = 0.33) [ 33 ]. In these studies
the range for successful stent placement was 87–100 %, portal pressure gradient
decrease was from 10 to 16.2 mmHg, and TIPS dysfunction was from 17 to 89 %
[ 33 ]. Zheng et al. also separated the studies assessing EVL from sclerotherapy, but
this did not change the outcomes [ 33 ].
Escorsell et al. compared quality of life in patients that received TIPS to endoscopic therapy for secondary prophylaxis. While there was a small trend towards
improvement in quality of life after both interventions, there were no signifi cant
differences between the TIPS and endoscopic therapy groups [ 16 ]. This might be
explained by increased incidence of hepatic encephalopathy in the TIPS group
being offset by decreased incidence of variceal bleeding. Two controlled studies
compared costs of TIPS to medical management with confl icting results [ 16 , 19 ].
The cost of TIPS in these studies varied from $11,294 to $21,603. A number of
cost-effectiveness analyses on TIPS and medical therapy for secondary prophylaxis
have been conducted with varying results in determining the most cost effective
procedure [ 34 – 36 ]. This difference can likely be explained by the many variables
that will infl uence the cost such as the number of signifi cant rebleeds, endoscopic
technique and sessions required for eradication, variations in institutional procedural costs, the number of TIPS revisions required, complications, and the length of
follow up. The cost of TIPS is usually highest in the fi rst year and will decline subsequently if limited interventions are required. Closed stents will likely decrease the
cost with fewer revisions required [ 14 ].
Ascites
Ascites is initially managed non-invasively with diuretics and dietary changes.
Refractory cases may require paracentesis or TIPS . There are six randomized control trials (RCT) (Table 34.3 ) that have been performed comparing paracentesis ±
albumin to TIPS for treatment of refractory ascites [ 37 – 42 ]. All these studies con-
cluded that TIPS was superior to paracentesis for the control of refractory ascites as
well as improvement of renal function and hemodynamics. Results were inconsistent when it came to worsening hepatic encephalopathy and a mortality benefi t
[ 37 – 42 ]. These studies had methadologic variation present that contributed to the
differences in results, which included the number of participants, inclusion and
exclusion criteria, defi nitions of refractory ascites, volume of paracentesis, technical skills with TIPS, stents used, and follow up measurements.
Five of these studies were published before 2004 and fi ve meta-analysis between
2005 and 2007 analyzed the same results from these studies [
43 – 47 ]. There was
also great heterogeneity present in the results of these analyses. All analyses agreed
34 Management of Symptomatic Portal Hypertension: TIPS vs. Medical Management
384
that TIPS was signifi cantly superior to paracentesis and albumin in preventing
recurrence of ascites . However, hepatic encephalopathy was signifi cantly more
common in the TIPS group. Overall there was not a signifi cant mortality difference
between the two groups. The quality of the meta-analysis and systematic review
varied with a number of limitations.
The study by D’Amico et al. was one of the stronger meta-analysis [ 45 ]. They
excluded the initial trial by Lebrec as it was identifi ed as an outlier with the lowest
successful TIPS placement (77 %), the lowest portal pressure gradient decrease
(6 mmHg), the lowest secondary patency rates (46 %), and the only study showing
a signifi cantly increased mortality with TIPS placement (40 % vs 71 % p = 0.03)
[ 37 ]. The range of technical success in the four other studies was 89–100 %, reduc-
tion in portal pressure gradient was 10.4–14 mmHg, and secondary patency rates
were 82–93 %. Surgical shunts were rarely placed if TIPS could not be successfully
placed. After excluding this study from their analysis, the pooled odds ratio (OR)
for recurrence of ascites with TIPS was 0.14 (CI 0.07–0.27), the OR for hepatic
encephalopathy with TIPS was 2.26 (CI 1.35–3.76), and OR for mortality with
TIPS was 0.74 (CI 0.40–1.37) [ 45 ].
All RCTs had a subset of patients that underwent liver transplant ation after TIPS .
Salerno et al. performed a meta-analysis on the initial fi ve RCTs using individual
patient data from four RCTs evaluating the cumulative effects of transplant-free
Table 34.3 The main outcomes of studies for refractory ascites comparing medical management
( paracentesis ±albumin ± salt restriction ± diuretics ) to TIPS
Study (year)
Study type
( quality of
evidence)
Patients
(C vs. T)
Ascites
recurrence
(C vs. T)
Hepatic
encephalopathy (C
vs. T)
Mortality (C
vs. T)
Lebrec
(1996)
RCT
(moderate)
12 vs. 13 92 % vs.
77 %
0 % vs. 23 % 40 % vs
71 %
p=n.s p=n.s p = 0.03
Rossle
(2000)
RCT (strong) 31 vs. 29 76 % vs.
21 %
48 % vs. 58 % 74 % vs.
52 %
p = 0.001 p=n.s p=n.s
Gines
(2002)
RCT (strong) 35 vs. 35 83 % vs.
49 %
66 % vs. 77 % 51 % vs
57 %
p = 0.003 p = 0.29 p = 0.6
Sanyal
(2003)
RCT (strong) 57 vs. 52 84 % vs.
42 %
19 % vs. 38 % 37 % vs.
40 %
p < 0.001 p = 0.058 p = 0.84
Salerno
(2004)
RCT (strong) 33 vs. 33 97 % vs.
39 %
39 % vs. 69 % 61 % vs.
39 %
p = 0.0012 p=n.s p = 0.021
Narahara
(2011)
RCT (strong) 30 vs. 30 80 % vs
13 %
17 % vs. 67 % 70 % vs.
57 %
p < 0.001 p < 0.001 p = 0.422
C control group (medical management ), T treatment groups ( TIPS ), RCT randomized control trial,
n.s not shown
A. Teriaky and A. Aronsohn
385
survival [ 47 ]. The actuarial probability of transplant free survival was signifi cantly
better in the TIPS groups (p = 0.035). The average transplant free survival at 1, 2,
and 3 years was 63.1 %, 49.0 %, and 38.1 % for the TIPS group and 52.5 %, 35.2 %,
and 28.7 % for the paracentesis group. MELD scores did not alter the mortality difference seen between the TIPS and paracentesis groups. Multivariate analysis identifi ed older age, high bilirubin, low plasma sodium, and treatment allocation as
predictors of death [ 47 ].
Quality of life for TIPS versus paracentesis was only assessed by Sanyal et al.
[ 40 ]. The SF-36 questionnaire, consisting of a physical and mental component, was
used in both groups before and after the interventions. While the scale score
improved signifi cantly amongst both arms after the interventions, there was no signifi cant difference in quality of life between the paracentesis and TIPS group [ 40 ,
48 ]. The lack of a signifi cant change in quality of life may be due to the fact that
while ascites may improve with TIPS, hepatic encephalopathy may worsen.
Gines et al. showed that the calculated accumulated cost of TIPS was greater in
both the United States and Spain per patient at respectively 103 % and 41 % the cost
in the paracentesis and albumin group. In the United States the total cost per patient
in the TIPS group was $19,813 and $9,765 for the paracentesis and albumin group
[ 39 ]. The infl ated cost of TIPS was partially due to the open stents requiring multi-
ple revisions [ 14 ].
Other Manifestations of Portal Hypertension
Non-esophageal Varices
The evidence for TIPS in controlling other manifestations of PH is limited. First line
treatment for gastric variceal bleeding, which can be diffi cult to control, has involved
sclerotherapy with cyanoacrylate [ 11 ]. TIPS has been used as salvage therapy. A
single RCT by Lo et al showed that TIPS decreased rebleeding from gastric varices
compared to cyanoacrylate (11 % vs. 38 % p = 0.014) while worsening encephalopathy (26 % vs. 3 % P < 0.01) without a difference in mortality or other major
complications [ 49 ]. Uncontrolled trials showed that transfusion dependent portal
hypertensive gastropathy may improve with TIPS while gastric antral vascular ectasia does not [ 50 , 51 ]. Ectopic varices can occur along the gastrointestinal tract and
can bleed. Case studies have shown some benefi t with TIPS in reducing bleeding
[ 52 , 53 ].
Hepatic Hydrothorax
Uncontrolled trials have assessed the effi cacy of TIPS in hepatic hydrothorax. Singh
et al. reviewed eight of these studies, which included 332 patients. The mean
improvement in respiratory symptoms and complete and partial response rates to
34 Management of Symptomatic Portal Hypertension: TIPS vs. Medical Management
386
the resolution of the hydrothorax were 74 %, 55.9 % and 24.6 % respectively. The
average 30-day mortality , 1-year survival , and incidence of hepatic encephalopathy
were 18.6 %, 52.3 %, and 26.7 % respectively [ 54 ].
Hepatorenal Syndrome
The effi cacy of TIPS to manage patients with HRS type 1 and 2 has been studied in
a small number of uncontrolled trials. These studies have identifi ed that renal function, hemodynamics, and ascites can improve in select patients with low MELD and
Child-Pugh scores undergoing TIPS, but are not powered to show a survival benefi t
[ 55 – 58 ].
Other
TIPS had been used in the treatment of Budd-Chiari syndrome. A retrospective
study of 221 patients showed that TIPS could be successfully used after failure of
medical therapy in appropriately selected patients [ 59 ]. Small case studies have
looked at the use of TIPS in sinuosoidal obstruction syndrome. While there was an
improvement in ascites , most patients still died [ 60 ]. Very little literature exists for
TIPS in hepatopulmonary syndrome to support its use and portopulmonary hypertension is a contraindication to TIPS [ 61 ].
Recommendations
• TIPS is superior to medical management in preventing recurrent variceal bleed-
ing and recurrent ascites while worsening hepatic encephalopathy (evidence
quality high; strong recommendation).
• TIPS may improve mortality in well-selected patients with variceal hemorrhage
or refractory ascites (evidence quality moderate; recommendation moderate).
• TIPS may have some utility in other manifestations of PH (evidence quality low;
recommendation low).
A Personal View of the Data
TIPS has an important role to play in variceal hemorrhage and refractory ascites . It
decreases rebleeding and ascites while worsening encephalopathy. It has not consistently shown a mortality benefi t, but has displayed a benefi t in specifi c circumstances. However, the technology of TIPS has evolved with closed stents, which
have been shown to be superior to open stents with lower rates of occlusion without
A. Teriaky and A. Aronsohn
387
worsening encephalopathy [ 14 ]. Most of the literature has not been done using the
closed stent and since this is a newer technology, studies will need to be repeated to
see if this changes outcomes . Further studies are also required to study the other
manifestations of PH.
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A. Teriaky and A. Aronsohn
391© Springer International Publishing Switzerland 2016
J.M. Millis, J.B. Matthews (eds.), Diffi cult Decisions in Hepatobiliary
and Pancreatic Surgery, Diffi cult Decisions in Surgery: An Evidence-Based
Approach, DOI 10.1007/978-3-319-27365-5_35
Chapter 35
Should All Hepatic Arteriovenous Fistulas
Be Embolized?
Darren van Beek and Brian Funaki
Abstract Hepatic arteriovenous fi stulae (AVF) are rare but increasingly encountered
clinical entities. Due to their poorly understood natural history and multiple underlying etiologies, treatment currently represents a clinical quandary. There are no
defi nitive studies regarding management, but rather, only small published case
series. A better understanding of the underlying mechanisms of AVF formation, factors affecting clinical signifi cance, and knowledge of the risks and benefi ts of treatment can help guide physicians in their management of this complex clinical
dilemma.
Keywords Arteriovenous fi stula • Arterioportal fi stula • Embolization • Hepatic
transplant
Introduction
A hepatic arteriovenous fi stula (AVF) is a rare clinical entity that has been increasingly diagnosed in recent decades. As the natural history and management options
are unclear, it poses a diagnostic dilemma for clinicians.
Part of the confusion regarding a hepatic AVF arises from the fact that it is a
catch-all term for multiple pathophysiologic entities arising from numerous underlying causes. Anatomically, this group can be divided into intrahepatic and extrahepatic shunts. Much of the early literature on the topic focused on extrahepatic shunts
between the visceral arterial and portal venous systems. A review published in 1987
showed 30 cases of fi stulas between the arterial and portal venous systems, of which
only 3 were intrahepatic [ 1 , 2 ]. Some authors have speculated that this early reported
D. van Beek • B. Funaki (*)
Department of Radiology, Section of Vascular and Interventional Radiology ,
University of Chicago Medical Center , 5841 S. Maryland Avenue MC 2026,
Room Q-219 , Chicago , IL 60637 , USA
e-mail:
bfunaki@radiology.bsd.uchicago.edu