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Portal
Hypertension
Clifford S. Cho,
MD
Fellow, Department of Surgical Oncology
Memorial Sloan-Kettering Cancer Center
Layton F.
Rikkers, MD, FACS
A.R.
Curreri Professor and Chairman, Department of Surgery
University of Wisconsin Medical School
http://www.acssurgery.com/acsonline/chapters/ch0510.htm
Clinical strategies for managing portal hypertension have
undergone significant refinements over the past half-century.
This evolution has been driven by advances in our understanding
of the physiology of both the disease and the therapies employed
against it. Today, clinical management of the portal
hypertensive patient is a truly multidisciplinary endeavor,
requiring the coordinated efforts of skilled intensivists,
gastroenterologists, hepatologists, interventional radiologists,
and surgeons. Nevertheless, portal hypertension and its manifold
complications remain some of the most vexing problems
encountered in modern medicine and surgery.
In this chapter, we briefly review portal venous anatomy and
the pathophysiology of portal hypertension [see Sidebar
Portal Hypertension: Anatomic and Physiologic Considerations];
however, our main focus is on current practical approaches to
managing portal hypertension and its associated sequelae
(variceal bleeding, ascites, and hepatic encephalopathy). Of
particular relevance to surgeons is that the role of surgical
therapy has shifted significantly. Operative treatment now
occupies only the final steps in modern treatment protocols for
portal hypertension—that is, it serves as a form of salvage for
intractable cases that are refractory to other forms of therapy.
Clinical
Evaluation
The ultimate aims of diagnostic evaluation in a patient with
portal hypertension are (1) to determine the cause of portal
hypertension [see Table 1], (2) to estimate hepatic
functional reserve, (3) to define the portal venous anatomy and
assess hemodynamic status, and (4) to identify the site of GI
hemorrhage (if present). Any history of chronic alcohol abuse,
hepatitis, or exposure to hepatotoxins raises the suspicion of
cirrhotic liver disease. Confirmatory evidence of chronic liver
disease on physical examination may be found in the form of
jaundice, chest wall spider angiomata, palmar erythema,
Dupuytren contractures, testicular atrophy, or gynecomastia.
Ascites, splenomegaly, caput medusae, encephalopathic
alterations in mental status, and asterixis are all suggestive
of portal hypertension.
Investigative
Studies
Laboratory studies can also provide indicators of hepatic
dysfunction. The hypersplenism that often accompanies cirrhosis
can produce mild to moderate pancytopenia. Anemia may also
reflect variceal hemorrhage, hemolysis, or simply the chronic
malnutrition or bone-marrow suppression associated with chronic
alcoholism. Associated hyperaldosteronism, emesis, or diarrhea
may give rise to electrolyte derangements, including
hyponatremia, hypokalemia, metabolic alkalosis, and prerenal
azotemia. Coagulopathy is usually attributable to chronic
deficiencies in clotting factors that are normally synthesized
by the liver; thus, elevation of the prothrombin time (PT) or
the international normalized ratio (INR) often reflects the
degree of chronic hepatic impairment. Similarly, the degree of
hyperbilirubinemia can be a measure of both acute and chronic
hepatic dysfunction. Hepatocellular necrosis results in marked
elevations in serum aminotransferases that are readily observed
in patients with chronic active viral or alcoholic hepatitis. An
alanine aminotransferase (ALT)-aspartate aminotransferase (AST)
ratio of 2 or higher is often seen in patients with alcoholic
liver disease.
The Child-Pugh scoring system is a useful tool for
quantifying hepatic functional reserve [see Table 2].1
Based on total bilirubin and albumin levels, PT (INR), and the
clinical severity of ascites and hepatic encephalopathy, the
Child-Pugh score predicts both the likelihood of variceal
hemorrhage and its anticipated mortality. A newer assessment
tool, the Model for End-Stage Liver Disease (MELD) scoring
system, which takes the degree of renal impairment and the cause
of hepatic dysfunction into account, has also been used to
predict outcomes in cirrhotic patients.2
Management of
Variceal Bleeding
The prognosis of variceal hemorrhage depends on the presence
or absence of underlying cirrhosis. In noncirrhotic patients,
the mortality associated with a first episode of variceal
hemorrhage ranges from 5% to 10%; in cirrhotic patients, the
range is from 40% to 70%. Esophagogastric varices ultimately
develop in approximately one half of cirrhotic patients, and
bleeding episodes occur in approximately one third of cirrhotic
patients with varices. If the initial hemorrhagic episode
resolves spontaneously, 30% of patients experience rebleeding
within 6 weeks, and 70% experience rebleeding within 1 year. It
is noteworthy that overall mortality in patients who survive 6
weeks after an episode of variceal bleeding is statistically
indistinguishable from that in persons who have never
experienced such an episode.
Further risk stratification is based on the extent of hepatic
decompensation. The mortality associated with variceal
hemorrhage is 5% for patients with Child class A cirrhosis, 25%
for those with Child class B cirrhosis, and over 50% for those
with Child class C cirrhosis. The likelihood of recurrent
hemorrhage is 28% for patients with Child class A cirrhosis, 48%
for those with Child class B cirrhosis, and 68% for those with
Child class C cirrhosis.3
Treatment
of Acute Variceal Hemorrhage
Section 5 / Chapter 10 - Portal
Hypertension
Figure 1. Treatment of acute variceal
bleeding
Algorithm outlines treatment of acute
variceal bleeding.
Management of acute variceal hemorrhage [see Figure 1]
begins with the establishment of adequate airway protection. The
risk of aspiration and consequent respiratory deterioration is
particularly high among patients with hepatic encephalopathy and
those undergoing endoscopic therapy. Accordingly, the threshold
for early endotracheal intubation should be low, particularly if
endosopic therapy is considered. As with all cases of brisk
hemorrhage, adequate venous access is mandatory; placement of a
central venous catheter for accurate volume assessment is
particularly useful in cases of major bleeding. The presence of
chronic liver disease often necessitates vigorous replacement of
circulatory volume and coagulation factors, often involving
infusion of colloids and transfusion of fresh frozen plasma and
packed red blood cells. Antibiotic prophylaxis therapy is
recommended because of the propensity of bacterial infections to
develop in patients with chronic liver disease after bleeding
episodes.
Pharmacologic Therapy
First-line pharmacotherapy for acute variceal bleeding relies
on the long-acting somatostatin analogue octreotide, which has
been shown to decrease splanchnic blood flow and portal venous
pressure. Octreotide is administered in a 250 µg I.V. bolus,
followed by infusion of 25 to 50 µg/hr for 2 to 4 days.4
In addition, vasopressin, a strong splanchnic vasoconstrictor,
has been shown to control approximately 50% of acute variceal
bleeding episodes.4,5
Vasopressin is typically administered in a 20 U I.V. bolus over
20 minutes, followed by infusion of 0.2 to 0.4 U/min. The
therapeutic benefits of octreotide and vasopressin appear to be
similar, though the side-effect profile of octreotide appears to
be much lower than that of vasopressin monotherapy.4
Adjunctive use of nitroglycerin at an initial rate of 50 µg/min
(titrated according to blood pressure tolerance) effectively
reduces the cardiac complications of vasopressin and thereby
facilitates its administration.6
The long-acting vasopressin analogue terlipressin has been shown
to be approximately as effective as octreotide.7
Endoscopic Therapy
Endoscopic treatment, in the form of sclerosant injection or
band ligation, has become a standard form of therapy for acute
variceal hemorrhage. Experienced endoscopists achieve initial
control of hemorrhage in 74% to 95% of cases; however,
rebleeding rates ranging from 20% to 50% are typically observed.
In endoscopic sclerotherapy, a sclerosant—typically either 5%
sodium morrhuate (more common in the United States) or 5%
ethanolamine oleate (more common in Europe and Japan)—is
injected either intravariceally to obliterate the varix or
paravariceally to induce submucosal fibrosis and thereby prevent
variceal rupture. Three prospective, randomized, controlled
trials demonstrated that endoscopic sclerotherapy, compared with
traditional balloon tamponade, achieved better initial
hemorrhage control, resulted in fewer episodes of rebleeding,
and, in selected cohorts of patients, led to improved long-term
survival.8–10
Furthermore, routine use of balloon tamponade after
sclerotherapy appeared not to confer any additional therapeutic
benefit.8
There are, however, significant risks associated with the use of
endoscopic sclerotherapy, including pulmonary complications,
transient chest pain, esophageal stricture formation with
recurrent sclerotherapy, iatrogenic portal vein thrombosis,
hemorrhagic esophageal ulceration, bacteremia, and esophageal
perforation.11
Partially in response to the potential complications of
endoscopic sclerotherapy, endoscopic variceal band ligation has
been advocated as a sclerosant-free therapeutic alternative. The
limited data comparing the two approaches suggest a trend toward
fewer rebleeding episodes, fewer endoscopic interventions, and
significantly lower procedure-related morbidity and overall
mortality after variceal ligation.12
Pharmacologic versus Endoscopic
Therapy
Two meta-analyses compared medical pharmacotherapy with
emergency sclerotherapy as first-line treatment of acute
variceal hemorrhage.13,14
No significant differences between the two approaches were
demonstrated with respect to initial hemorrhage control or
mortality, though treatment-related complications appeared to be
significantly more common after sclerotherapy. On the basis of
these studies, it has been suggested that endoscopic treatment
should be reserved for cases of pharmacotherapeutic failure or
that pharmacologic therapy should be initiated in situations
where endoscopy is not immediately available. At present,
however, it is more common for the two forms of treatment to be
employed concurrently. Pharmacotherapy is often initiated in
preparation for endoscopy; early mitigation or control of
variceal hemorrhage can make endoscopic visualization and
intervention easier, safer, and more effective. Indeed,
administration of somatostatin before and after endoscopic
sclerotherapy has been shown to improve treatment efficacy and
decrease transfusion requirements in comparison with endoscopic
sclerotherapy alone.15,16
Balloon Tamponade
Section 5 / Chapter 10 - Portal
Hypertension
Figure 2. Sengstaken-Blakemore tube
The Sengstaken-Blakemore tube permits
tamponade of both the distal esophagus and the gastric fundus.
An accessory nasogastric tube permits aspiration of secretions
from above the esophageal balloon.
Although the devices used for balloon tamponade have evolved
through numerous different forms over the years, all of them
rely on the same basic principle—application of direct upward
pressure against varices at the esophagogastric junction.
Patients for whom balloon tamponade is considered should be
intubated endotracheally to prevent airway occlusion and
aspiration. The tube is inserted into the stomach, and the
gastric balloon is partially inflated with 40 to 50 ml of air [see
Figure 2]. An abdominal radiograph is obtained to ensure
that the gastric balloon is correctly positioned within the
stomach and below the diaphragm. This balloon is then further
inflated until it holds 300 ml of air, and the tube is pulled
upward with external traction. If hemorrhage is not controlled
at this point, the esophageal balloon is inflated to a pressure
of 35 to 40 mm Hg. Suction drainage is applied to both the
esophageal port and the gastric port to minimize aspiration risk
and monitor for recurrent hemorrhage.
When properly applied, direct tamponade therapy is 90%
effective in controlling acute hemorrhage. The primary
limitation of such therapy is that bleeding resumes in as many
as 50% of patients after takedown and removal of the balloon.
Furthermore, serious potential complications (e.g., gastric or
esophageal perforation, aspiration, and airway obstruction)
result in treatment-related mortalities as high as 20%.17,18
Nevertheless, in cases of brisk variceal hemorrhage refractory
to pharmacologic and endoscopic therapy, balloon tamponade may
have a role to play as a bridge therapy to more definitive forms
of treatment, such as transjugular intrahepatic portosystemic
shunting (TIPS) (see below) or operative intervention.
Transjugular Intrahepatic
Portosystemic Shunting
Section 5 / Chapter 10 - Portal
Hypertension
Figure 3. Procedure for performing TIPS
Depicted is the procedure for performing
TIPS. (a) A needle is passed under radiologic guidance
from a hepatic vein into a major portal venous branch, and a
guide wire is advanced through this needle. (b) A balloon
is passed over the guide wire, creating a tract in the hepatic
parenchyma. (c) An expandable stent is placed though this
tract. (d) The effective result is a nonselective
portosystemic shunt.
A nonoperative technique for creating an intrahepatic
portosystemic fistula for decompression of portal hypertension
was proposed in 196919
and first performed in 1982.20
As currently practiced, TIPS is performed by (1) cannulating a
hepatic vein (usually the right hepatic vein) via the internal
jugular vein, (2) passing a needle from the hepatic vein through
the liver parenchyma and into a portal vein branch, (3) passing
a guide wire through the needle, (4) dilating the needle tract
with a balloon passed over the guide wire, and (5) stenting the
tract to a desired diameter, thus effectively constructing a
nonselective side-to-side portosystemic shunt [see Figure 3].
Experience with TIPS in the setting of acute variceal
hemorrhage is limited. However, one meta-analysis of studies
comparing the efficacy of conventional endoscopic therapy (with
or without pharmacotherapy) with that of TIPS in treating acute
hemorrhagic episodes demonstrated a significant improvement in
hemorrhage control with TIPS.21
Unfortunately, this improvement came at the cost of increased
rates of hepatic encephalopathy as a consequence of the
nonselective shunting of portal venous flow into the systemic
venous circulation. Furthermore, the meta-analysis failed to
demonstrate a significant improvement in overall mortality with
TIPS.21
Given the relative paucity of data on the use of TIPS as
first-line therapy for acute variceal hemorrhage, it is logical
to recommend that TIPS be employed in cases of
pharmacotherapeutic and endoscopic failure; the efficacy of TIPS
as salvage therapy in this setting is well documented.22
Contraindications to TIPS include right heart failure and
polycystic liver disease. Portal vein thrombosis is a relative
contraindication.
Surgical Therapy
The role of surgical management in the treatment of acute
variceal bleeding has changed considerably over the past 50
years. At present, operative intervention is reserved for cases
that have proved refractory to pharmacotherapy, endoscopy,
balloon tamponade, and TIPS. Numerous operations have been
developed, each with its own merits and flaws.
Esophageal transection with an end-to-end anastomosis (EEA)
stapler has been employed as a means of interrupting blood flow
into bleeding esophageal varices. In this technique, the
esophagus is mobilized, and the EEA stapler is passed into the
distal esophagus through a gastrotomy. With care taken not to
injure the vagus nerves and the external periesophageal veins
that may be providing collateral venous drainage, a
full-thickness segment of the esophagus is transected. When this
technique is used on an emergency basis in a patient with
acutely bleeding varices, operative mortality is as high as 76%,
and the rate of operative complications (e.g., esophageal
perforation, stricture, esophagitis, and infection) is
approximately 26%.23
Accordingly, esophageal transection is not commonly advocated as
a useful form of surgical therapy for acutely bleeding
esophageal varices.
In contrast, portosystemic shunting operations have been
widely used to treat acute variceal hemorrhage. The largest
single body of data on this practice comes from Orloff and
associates,24
who reported remarkable outcomes—71% survival at 10 years—in 400
consecutive patients undergoing emergency portacaval shunt
operations (mostly side-to-side) over a 28-year period.
Unfortunately, these investigators' experience stands in stark
contrast to that of most other groups, who uniformly reported
operative mortalities of about 40% and 5-year survival rates of
about 30%.
Another potential drawback to urgent operative shunting is
the manipulation and dissection that are often necessary in the
region of the porta hepatis: these measures can result in
adhesions and scarring, which can complicate future orthotopic
liver transplantation. For this reason, some surgeons have
advocated using the mesocaval interposition shunt [see
Prevention of Recurrent Variceal Hemorrhage, Surgical Therapy,
Portosystemic Shunts, Nonselective Shunts, below] in the
emergency setting because of its ability to lower portal
pressure without complicating the hilar dissection that will be
necessary if transplantation is carried out later.25
In addition, surgeons familiar with the distal splenorenal shunt
(DSRS) can employ this selective shunt in some cases of acute
variceal hemorrhage unaccompanied by refractory ascites.
Prevention
of Recurrent Variceal Hemorrhage
Pharmacotherapy
Section 5 / Chapter 10 - Portal
Hypertension
Figure 4. Prevention of recurrent variceal
bleeding
Algorithm outlines prevention of recurrent
variceal bleeding.
Without further treatment, the likelihood that hemorrhage
will recur within 1 year after control of an acute episode of
variceal bleeding is approximately 70%.26
The pharmacologic maneuver that has been used most extensively
to prevent recurrent variceal bleeding [see Figure 4] is
nonselective beta-adrenergic blockade, most commonly with
propranolol. Although beta blockade has been shown to lower
portal pressure and hepatic vein wedge pressure, its ability to
induce this effect is variable and unpredictable.27
Nevertheless, a meta-analysis of multiple trials studying the
effectiveness of nonselective beta blockade demonstrated a
significant decline in recurrent bleeding and a trend toward
improved overall survival.4 Patients with
decompensated hepatic function appear to derive less benefit
from beta blockade, possibly because of the downregulation of
beta-adrenergic receptors associated with cirrhosis.28
Adjunctive use of the long-acting vasodilator isosorbide
5-mononitrate (ISMN) appears to potentiate the efficacy of
propranolol therapy.29
Endoscopic Therapy
Repeated endoscopic therapy with sclerosant injection or band
ligation has been advocated as a means of completely eradicating
esophageal varices. Once the varices are eliminated, routine
endoscopy is performed at 6- to 12-month intervals to prevent
recurrent hemorrhage. Compared with medical treatment, long-term
endoscopic therapy results in fewer rebleeding episodes.4
Nevertheless, approximately one half of endoscopically treated
patients eventually experience recurrent hemorrhage, usually
within the first year. Approximately one third of patients
treated with repeated endoscopy ultimately must be converted to
another form of therapy because of unrelenting major bleeding.30,31
For this reason, such extended endoscopic surveillance and
treatment should be reserved for compliant patients who live in
proximity to tertiary medical care and should be administered
with the understanding that conversion to a more definitive form
of therapy may be necessary if endoscopy fails.
Transjugular Intrahepatic
Portosystemic Shunting
TIPS [see Figure 3 ] has been employed to prevent
recurrent episodes of variceal hemorrhage, particularly as a
form of bridge therapy for patients awaiting orthotopic liver
transplantation. The potential advantage TIPS has over surgical
portosystemic shunting is the ability to decompress the portal
system without the risks associated with general anesthesia and
without postoperative complications. The major limitation of
TIPS is the shunt stenosis (caused by neointimal hyperplasia or
thrombosis) that occurs in as many as 50% of patients in the
first year after the procedure. Fortunately, most such episodes
of stenosis are amenable to balloon dilatation or secondary
shunt insertion; however, 10% to 15% of TIPS recipients
experience total shunt occlusion that cannot be reversed.
Furthermore, TIPS functions as a nonselective shunt, leading to
hepatic encephalopathy in approximately one third of patients.32
Meta-analytic comparison of TIPS with endoscopic therapy
indicates that rebleeding episodes are markedly reduced in
patients treated with TIPS, but at the cost of a higher
incidence of encephalopathy and a shunt malfunction rate of at
least 50%. That the efficacy of TIPS is relatively short-lived
makes this modality an ideal form of bridge therapy for patients
who are awaiting orthotopic liver transplantation or those who
have severe hepatic decompensation and thus are unlikely to live
long enough to experience failure of TIPS. TIPS can reduce the
number of bleeding episodes for patients on the transplant
waiting list. In addition, the significant reduction in portal
pressure produced by TIPS technically facilitates future liver
transplantation. Finally, unlike surgical shunts, TIPS is
completely removed at the time of recipient native hepatectomy.
Surgical Therapy
Surgical therapy is the most effective method of controlling
portal hypertension and preventing recurrent variceal
hemorrhage. The operative procedures available to the surgeon
have undergone numerous modifications and become more effective
over the years. Review of the surgical experience reveals that
with the onset of alternative modalities (e.g., TIPS and
transplantation), the risk status of patients undergoing
surgical therapy (as predicted by Child's classification) and
the frequency of emergency operations have steadily declined. As
a result, the incidence of postoperative hepatic encephalopathy
has gradually fallen and overall survival has gradually
improved.33
Surgical options for the prevention of recurrent variceal
hemorrhage in patients with portal hypertension may be divided
into three categories: (1) portosystemic shunt procedures, (2)
esophagogastric devascularization, and (3) orthotopic liver
transplantation.
Portosystemic shunts Surgical portosystemic shunting
provides a means of decompressing the hypertensive portal venous
system into the low-pressure systemic venous circulation.
Diversion of portal blood flow from the liver also deprives the
liver of important hepatotrophic hormones that are present in
portal venous blood while routing cerebral toxins normally
metabolized by the liver directly into the systemic circulation.
As a result, the primary complications of surgical portosystemic
shunting are accelerated hepatic dysfunction and hepatic
encephalopathy. Primarily in an attempt to minimize these
adverse sequelae, various forms of portosystemic shunting
operations have evolved, which may be classified as nonselective
shunts, selective shunts, or partial shunts.
Nonselective shunts
Section 5 / Chapter 10 - Portal
Hypertension
Figure 5. Portosystemic shunts
Nonselective portosystemic shunts either
immediately or eventually divert all portal blood flow from the
liver into the systemic venous circulation. Shown are the four
main variants: (a) end-to-side portacaval shunt, (b)
side-to-side portacaval shunt, (c) interposition shunt
(portacaval [1], mesocaval [2], and mesorenal [3]), and (d)
conventional (proximal) splenorenal shunt.
The classic nonselective portosystemic shunt is the
end-to-side portacaval shunt (the so-called Eck fistula) [see
Figure 5, part a]. This is the only nonselective shunt that
has been rigorously compared with conventional nonoperative
therapy. Several randomized, controlled trials demonstrated
superior control of bleeding after operative shunting: 9% to 25%
of patients experienced rebleeding after portacaval shunting
(mostly related to nonvariceal hemorrhage or shunt thrombosis),
whereas 65% to 98% of patients experienced rebleeding after
medical therapy.34–37
Markedly higher rates of spontaneous posttreatment
encephalopathy were reported in the operative shunt groups;
however, the overall rates of encephalopathy did not differ
between the operative groups and the medical groups, because the
encephalopathy seen in the medically treated patients (mainly
attributable to hemorrhage and infection) eventually became
equivalent to that seen in the surgically treated patients.
There were trends toward improved overall survival in the
surgical groups, but these trends did not attain statistical
significance.
The side-to-side portacaval shunt [see Figure 5, part b]
maintains the anatomic continuity of the portal vein as it
passes into the liver. However, the high sinusoidal resistance
typically present in the setting of cirrhosis effectively
renders this shunt a nonselective one, with no measurable
antegrade (i.e., hepatopedal) portal blood flow into the liver.
Consequently, the encephalopathy rates are no different from
those observed after end-to-side portacaval shunting.
Side-to-side portacaval shunting does offer the benefit of
decompressing the hepatic sinusoidal pressure via reversed
(i.e., hepatofugal) flow of blood from the liver into the portal
vein. Because transudation of interstitial fluid from both the
liver and the intestines is thought to contribute to ascites
formation, better control of ascites is achieved with a
side-to-side portacaval shunt, which effectively decompresses
both the splanchnic veins and the intrahepatic sinusoids, than
with an end-to-side portosystemic shunt, which decompresses only
the splanchnic veins. The side-to-side portacaval shunt is
therefore also recommended for patients with Budd-Chiari
syndrome, in whom an end-to-side portacaval shunt would not
relieve intrahepatic congestion resulting from hepatic venous
outflow occlusion. Otherwise, no significant outcome differences
between end-to-side and side-to-side portacaval shunts have been
documented. The end-to-side variant is, however, technically
easier to construct.
Placement of an interposition mesocaval shunt [see Figure
5, part c] composed of prosthetic or autogenous vein grafts
offers the technical advantages of avoiding hilar dissection
(thereby making future liver transplantation less complicated)
and permitting intentional shunt ligation in the event of
refractory postoperative encephalopathy. Like the side-to-side
portacaval shunt, the interposition shunt functions
physiologically as a nonselective shunt because of the
hepatofugal portal venous blood flow. The major drawback to the
interposition shunt is shunt thrombosis, which may develop in as
many as 35% of cases.
The conventional (proximal) splenorenal shunt [see Figure
5, part d] was initially advocated as a means of
decompressing portal venous flow while retaining hepatopedal
hepatic portal perfusion. This shunt is constructed by
performing a splenectomy and anastomosing the proximal splenic
vein to the left renal vein. Physiologic testing of patent
conventional splenorenal shunts suggests that they eventually
divert all portal flow into the renal vein and therefore
effectively function as nonselective shunts. Indeed, long-term
rates of hepatic encephalopathy appear to be no lower after
conventional splenorenal shunting than after portacaval
shunting.38
Shunt occlusion develops in about 18% of cases.39
In short, nonselective portosystemic shunts are an effective
means of controlling variceal hemorrhage in cases that are
refractory to other therapeutic approaches. Given the absence of
any major differences in the rate of encephalopathic
complications after the various nonselective shunts, the choice
of a nonselective shunting procedure should be based on the
surgeon's technical familiarity with the operations and on the
patient's candidacy for future transplantation. The end-to-side
portacaval shunt can be constructed relatively quickly but
should be avoided in patients who have intractable ascites or
Budd-Chiari syndrome and those who may subsequently undergo
liver transplantation. The side-to-side portacaval shunt may
provide better control of ascites but is technically more
challenging to construct and should also be avoided if future
transplantation is an option. The interposition mesocaval shunt
is relatively easy to construct and avoids hepatic hilar
dissection but is associated with a relatively high rate of
shunt occlusion when a nonautogenous conduit is used. The
conventional splenorenal shunt also avoids hilar dissection but
is associated with a high shunt occlusion rate and is
technically challenging to construct.
Selective shunts
Section 5 / Chapter 10 - Portal
Hypertension
Figure 6. Distal splenorenal shunt
The distal splenorenal shunt diverts portal
flow from the spleen and short gastric veins into the left renal
vein. The DSRS provides selective shunting by preserving portal
flow from the mesenteric circulation. Potential sites of
collateralization (e.g., the left gastric vein, the
gastroepiploic vein, and the umbilical vein) are routinely
interrupted to preserve hepatopedal portal flow.
In response to the postoperative complications seen after
nonselective portosystemic shunting (hepatic encephalopathy and
hepatic failure), Warren and colleagues introduced the distal
splenorenal shunt in 1967.40
The DSRS has become the prototypical selective shunt, in that it
selectively decompresses the esophagogastric veins while
maintaining hepatopedal flow from the mesenteric veins. It is
performed by anastomosing the distal splenic vein to the left
renal vein and interrupting venous collaterals (e.g., the left
gastric and right gastroepiploic veins) [see Figure 6].
As a result, the DSRS effectively separates the portal system
into two components: (1) a decompressed esophagogastric venous
circuit and (2) a persistently hypertensive mesenteric venous
circuit that continues to provide hepatopedal portal flow. Thus,
the DSRS does not address the mesenteric and sinusoidal
hypertension that is responsible for ascites formation. Indeed,
it is believed that the extensive retroperitoneal dissection
required to construct this shunt may actually contribute to
ascites formation through inadvertent disruption of
retroperitoneal lymphatic vessels. The DSRS is contraindicated
in patients who have refractory ascites or splenic vein
thrombosis, those who have previously undergone splenectomy, and
those with an excessively small (< 7 mm) splenic vein diameter.
Unfortunately, perfusion studies indicate that approximately
one half of patients lose hepatopedal flow within 1 year after a
DSRS procedure. This is a particular problem in patients with
alcoholic cirrhosis. The loss of shunt selectivity is believed
to result from progressive collateral diversion of portal flow
into the splenic vein via a network of pancreatic and
peripancreatic veins (the so-called pancreatic siphon effect).
Extensive skeletonization of the splenic vein off the pancreas
(so-called splenopancreatic disconnection) has been proposed as
a means of minimizing this unwanted collateralization,41
but at present, the evidence is insufficient to support routine
employment of this measure.
The complications of DSRS procedures are well described.
Depending on patient selection, postoperative ascites formation
is seen in 7% to 98% of cases; however, in only 0% to 14% of
cases is ascites clinically significant and refractory to
dietary sodium restriction and diuresis.23
Hepatic encephalopathy is reported in 0% to 32% of cases;
several clinical trials comparing DSRS with nonselective
shunting demonstrated significantly lower rates of
encephalopathy after DSRS, whereas other trials found no
statistically significant difference. With respect to overall
survival and hemorrhage control, DSRS and nonselective shunts
appear to be equivalent.42
Comparison of DSRS construction with endoscopic therapy has
yielded interesting results. Two controlled trials comparing
endoscopic therapy and salvage DSRS with early DSRS alone
demonstrated superior hemorrhage control with early DSRS.30,31
Rates of hepatic encephalopathy did not differ between the two
groups. One of the trials, conducted in an urban-suburban area
where 85% of sclerotherapy failures could be rescued with
salvage DSRS, found survival to be improved in patients treated
with endoscopic therapy and salvage DSRS, compared with survival
in patients treated with early DSRS alone.30
The other, performed in a less densely populated region where
only 31% of sclerotherapy failures could be rescued with salvage
DSRS, found survival to be improved in the early DSRS group.31
These data suggest that early definitive surgical intervention
may be preferable for patients who are too far from a tertiary
medical center to be able to reach one expeditiously in the
event of uncontrollable hemorrhage.
Attention is now being turned toward comparisons between the
DSRS and TIPS. One uncontrolled comparative study found that
with DSRS, hemorrhage control was better, the encephalopathy
rate was lower, and shunt occlusion was reduced, but the
incidence of postoperative ascites was higher.43
A National Institutes of Health-sponsored randomized comparison
between DSRS and TIPS is currently under way at multiple
centers.
The other main form of selective portosystemic shunt is the
coronary-caval shunt, initially described in Japan in 1984.44
This shunt is constructed by anastomosing an interposition graft
to the left gastric (coronary) vein on one end and the inferior
vena cava on the other. To date, the applicability of this
procedure has been limited, and most surgeons have relatively
little experience with it.
Partial shunts Various small-diameter interposition
portosystemic shunts have been proposed as partial shunts,
designed to achieve partial decompression of the entire portal
venous system while maintaining a degree of hepatopedal portal
flow to the liver. The most successful of these partial shunts
has been the small-diameter portacaval interposition shunt. The
use of a 10 mm or smaller interposition shunt, combined with
extensive disruption of portosystemic collateral venous
circuits, serves to maintain some degree of hepatic portal
perfusion. Early experience with the 8 mm ringed
polytetrafluoroethylene graft suggests that hepatic
encephalopathy rates are lower with this shunt than with
nonselective 16 mm grafts and that use of the smaller shunt
yields comparable long-term survival.45
An early comparison of the small-diameter portacaval shunt with
TIPS demonstrated lower rates of shunt occlusion and treatment
failure in the operative therapy group.46
Esophagogastric devascularization
Section 5 / Chapter 10 - Portal
Hypertension
Figure 7. Modified Sugiura procedure
Shown is the modified Sugiura procedure. By
extensively devascularizing the esophagogastric junction, this
procedure may provide a means of interrupting esophagogastric
varices without portosystemic shunting.
The most effective nonshunt operation for preventing
recurrent variceal hemorrhage is esophagogastric
devascularization with esophageal transection and splenectomy,
as advocated by Sugiura and associates.47
Unlike simple esophageal transection, which has been used with
limited success in the setting of acute hemorrhage, the Sugiura
procedure and its subsequent modifications [see Figure 7]
involve ligation of venous branches entering the distal
esophagus and the proximal stomach from the level of the
inferior pulmonary vein, combined with selective vagotomy and
pyloroplasty [see 5:20 Gastroduodenal Procedures]. A key
point is that the left gastric (coronary) vein and the
paraesophageal collateral veins are preserved to permit
portoazygous collateralization, which inhibits future varix
formation. Initial reports from Japan cited a 5.2% operative
mortality and a 6.3% rate of recurrent hemorrhage (most often
from nonvariceal causes).47,48
Unfortunately, these successes have not been easily replicated
in the United States, where operative mortality with this
procedure has exceeded 20%, with bleeding recurring in 35% to
55% of patients.49,50
Nevertheless, modifications of the Sugiura procedure continue to
be performed in patients who are unable to undergo shunting
procedures because of extensive splanchnic vein thrombosis.
Orthotopic liver transplantation Orthotopic liver
transplantation is the most definitive form of therapy for
complications of portal hypertension. The cost of cadaveric and
living-donor liver transplantation and its attendant
immunosuppression, as well as the paucity of available
allografts, make liver replacement an option for only a select
minority of patients presenting with portal hypertensive
sequelae. Accordingly, careful analysis of the outcomes of
transplantation procedures in comparison with those of
nontransplantation procedures is necessary for optimal
allocation of this limited resource.
For patients whose portal hypertension has become refractory
to nonoperative management strategies, the decision whether to
employ transplantation or nontransplantation operative therapy
can be based on the level of hepatic functional reserve.
Patients with Child class A or mild class B cirrhosis appear to
do well with nontransplantation therapy as first-line operative
treatment, with the understanding that liver transplantation may
remain an option for salvage therapy in the event of future
hepatic functional deterioration. In contrast, patients with
more advanced Child class B or Child class C cirrhosis appear to
benefit from early transplantation, with nonoperative strategies
employed strictly as bridge therapy for maintenance during the
time spent on the allograft waiting list.51,52
Prophylaxis of Initial Variceal Hemorrhage
The significant mortality associated with variceal hemorrhage
has prompted efforts to devise effective means of preventing the
onset of initial variceal bleeding. The difficulty of
identifying those 20% to 33% of cirrhotic patients who will
experience bleeding episodes remains the primary challenge in
the application of prophylaxis for variceal hemorrhage. Patient
characteristics that predict an increased likelihood of variceal
bleeding include alcoholic cirrhosis, active alcohol
consumption, and severe hepatic dysfunction.53
Certain anatomic features of varices seen at the time of
endoscopic examination have been shown to predict the likelihood
of rupture: evidence of variceal wall thinning (cherry-red
spots, red wales), variceal tortuosity, superimposition of
varices on other varices, and the presence of gastric varices
all appear to be correlated with a higher likelihood of
hemorrhage.54
At present, pharmacologic therapy is the only measure that
provides effective prophylaxis against variceal hemorrhage.
Nonselective beta-adrenergic blockade, either with propranolol
or the long-acting agent nadolol, reduces portal venous pressure
by decreasing cardiac output and favoring splanchnic
vasoconstriction. Clinical trials examining the efficacy of
propranolol therapy demonstrated lowered rates of initial
variceal bleeding, though the ultimate influence of beta
blockade on patient survival was mixed.55–57
Endoscopic sclerotherapy has not been consistently effective
in preventing initial variceal bleeding. In fact, several trials
found survival to be poorer in patients treated with
prophylactic sclerotherapy than in those managed with
prophylactic pharmacotherapy.4,58
This difference is probably attributable to the well-documented
complications associated with endoscopic sclerotherapy.
The flaws of prophylactic endoscopic sclerotherapy have led
some authorities to advocate endoscopic variceal band ligation
as a more effective form of prophylaxis. One trial demonstrated
that variceal band ligation achieved better prophylaxis of
initial variceal bleeding than propranolol therapy did.59
Clearly, this observation warrants further investigation.
Early trials comparing prophylactic portosystemic shunting
with medical prophylaxis definitively showed that early
operative intervention conferred no significant benefit. In
fact, the significant morbidity associated with surgical
shunting and the substantial risk of accelerated hepatic
dysfunction and encephalopathy led to lower survival rates in
patients treated with prophylactic surgical procedures.6,60
At present, the data are insufficient to recommend the use of
prophylactic TIPS to prevent acute variceal hemorrhage.
Management of
Ascites
The presence of ascites in a patient with portal hypertension
is typically an ominous finding that is of significant
prognostic importance: 1-year mortalities as high as 50% have
been reported in cirrhotic patients with new-onset ascites,
whereas baseline 1-year mortalities in cirrhotic patients
without ascites are in the range of 10%.61
The pathogenesis of ascites formation appears to be related to
the relative hypovolemia and the primary avidity of renal sodium
retention that develop in patients with cirrhosis. Hypovolemia
induces renin-angiotensin activation and salt and water
reabsorption, which, in the setting of chronic liver
dysfunction, results in excessive transudation of fluid out of
the liver and the intestines and into the peritoneal cavity. The
major complications of this process are spontaneous bacterial
peritonitis (SBP) and hepatorenal syndrome (HRS) [see
Complications, below], which account for the bulk of the
morbidity and mortality associated with ascites in patients with
portal hypertension.
Nonsurgical Therapy
By addressing the hyperavidity of sodium retention that
drives much of ascites formation, restriction of dietary salt
intake (to levels as low as 2 g of sodium a day) can resolve
ascites in approximately 25% of cases. The hyperaldosteronemic
state that exists can be countered by initiating diuresis with
spironolactone, which, at dosages ranging from 100 to 400
mg/day, can relieve ascites in an additional 60% to 70% of
patients. Although automatic addition of loop diuretics has not
been proved to enhance the clinical efficacy of spironolactone,
augmentation of spironolactone therapy with furosemide can be
helpful for patients whose ascites is refractory to
spironolactone monotherapy or who have hyperkalemia as a result
of spironolactone treatment. Gradual diuresis is necessary to
prevent potential complications (e.g., prerenal azotemia and
HRS).62
In cases of ascites that is refractory to medical dietary
restriction and diuretic therapy, large-volume paracentesis has
been employed with some success. Albumin is typically infused at
a dose of 6 to 8 g per liter of ascitic fluid to prevent the
hypotension that results from acute volume shifts. Patients in
whom ascites recurs after multiple rounds of large-volume
paracentesis should be considered for TIPS. TIPS is particularly
useful in patients with ascites and a history of bleeding
esophageal varices; it corrects as many as 80% of medically
refractory cases of ascites.63
However, the efficacy of TIPS is counterbalanced by its
attendant risks (i.e., hepatic encephalopathy, shunt occlusion,
and accelerated hepatic failure), especially in patients with
poor hepatic functional reserve.
Surgical
Therapy
Operative intervention plays only a limited role in the
management of ascites. Surgically inserted peritoneovenous
shunts have been compared with large-volume paracentesis in
patients with ascites refractory to medical therapy. No
significant differences in early control of ascites have been
detected, but patients treated with peritoneovenous shunting
appear to benefit from faster ascites resolution, longer
palliation, and fewer hospital readmissions.64
Long-term follow-up, however, indicates that shunt occlusion
occurs in 47% of patients so treated and disseminated
intravascular coagulation in as many as 35%.
The morbidity and mortality associated with operative therapy
make routine use of side-to-side portacaval shunts a poor option
for managing ascites. The exceptions to this general statement
are cases in which ascites proves refractory to medical and TIPS
therapy or in which concomitant refractory variceal hemorrhage
is present.
Complications
SBP is the most common form of ascitic infection. It
typically is signaled by fever and abdominal tenderness and
often is also accompanied by acute hepatic and renal
deterioration. The diagnosis is generally made by analyzing
ascitic fluid collected through paracentesis and is defined by
the presence of a positive bacterial culture and a neutrophil
count higher than 250/mm3 in the absence of an
obvious intra-abdominal source of infection. Unlike secondary
peritonitis, SBP is typically monomicrobial, and the frequency
with which enteric gram-negative rods are found with SBP
suggests intestinal bacterial translocation as a potential
cause. SBP carries a mortality of 25% and should therefore be
treated aggressively with I.V. antibiotic therapy. Given the 70%
recurrence rate after an initial episode of SBP, continuation of
suppressive antimicrobial therapy until ascites resolves is
warranted.65
HRS, a poorly understood state characterized by progressive
and refractory renal impairment, typically occurs in the setting
of tense ascites and hepatic disease. Management of HRS is
strictly supportive, in that the syndrome often responds only to
correction of the underlying liver dysfunction. Accordingly, the
only proven therapy for HRS is liver transplantation.
Management of
Hepatic Encephalopathy
Hepatic encephalopathy is a complex of symptoms characterized
by mental status changes ranging from impaired mentation to
frank stupor. The classic neurologic finding associated with
this symptom complex is asterixis. Typically, hepatic
encephalopathy develops in the setting of significant
portosystemic shunting or significant hepatic functional
impairment. It is most commonly observed after the creation of a
therapeutic nonselective portosystemic shunt. Its onset is
usually precipitated by dehydration, GI hemorrhage, sepsis, or
excessive protein intake; in fact, the spontaneous development
of hepatic encephalopathy mandates work-up for these physiologic
triggers. It has been speculated that the shunting of
intestinally absorbed cerebral toxins (e.g., ammonia,
mercaptans, and g-aminobutyric
acid) away from hepatic metabolism is what causes hepatic
encephalopathy; however, the absolute level of circulating
ammonia correlates poorly with the magnitude of encephalopathic
symptoms.
Correction of the triggers that cause hepatic encephalopathy
often reverses the psychoneurologic disturbances. In severe
cases, patients should also receive neomycin (1.5 g every 6
hours), which covers enteric urease-positive bacteria, and
lactulose (20 to 30 g two to four times daily), a disaccharide
GI cathartic. Both agents are believed to reduce intestinal
levels of ammonia and inhibit its enteric absorption. Whereas
neomycin has long-term side effects (i.e., nephrotoxicity and
ototoxicity), long-term lactulose therapy is generally well
tolerated. Dietary protein restriction should also be employed
for long-term suppression of hepatic encephalopathy. On
occasion, refractory cases of shunt-induced hepatic
encephalopathy may be treated by means of intentional ligation
or occlusion of the portosystemic shunt.
Acknowledgments
Figure 2 Carol
Donner.
Figures 3 and 5
through 7 Alice Y. Chen.
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