Chapter 47. Portal Hypertension

Portal hypertension is present when portal venous pressure exceeds 10 mm Hg. This chapter addresses the causes, evaluation, and treatment options for patients with portal hypertension. While the emphasis is on surgical aspects, this group of patients requires a multidisciplinary approach and surgical therapy must inevitably be viewed in this context. The major clinical presentations that will be addressed are variceal bleeding, ascites, end-stage liver disease, and the pulmonary syndromes. Whatever the presentation of portal hypertension, be it an incidental finding or one of the above clinical presentations, it demands full investigation. In the United States, the etiology is most commonly cirrhosis, but other etiologies such as prehepatic portal or splenic vein thrombosis or other intraparenchymal liver disease such as schistosomiasis or hepatic fibrosis should be considered. Definition of the cause is important as prognosis depends on the underlying liver disease, and a full evaluation to allow development of a treatment plan for variceal bleeding, ascites, or end-stage liver disease is paramount at initial presentation. The focus of this chapter is on emphasizing the role of a multidisciplinary team approach to managing patients with portal hypertension.

Portal hypertension was recognized by the Greeks1,2, was highlighted by Shakespeare in his character of Falstaff, and has played a role through much of history. The evolution of the treatment of portal hypertension was driven by surgeons until the 1980s. Nicolai Eck, a Russian Army surgeon, performed an end-to-side portacaval shunt in 1883 in an animal model. Pavlov, the great Russian physiologist, conducted animal studies that showed the detrimental effect of diverting portal flow, describing meat intoxication (encephalopathy) and liver failure. Vidal, a French surgeon is credited with performing the first portal systemic shunt in a human in 1903. Morison and Talma operated on patients with portal hypertension with procedures such as omentopexy and splenic transposition, but their failure to recognize cirrhosis as the cause of portal hypertension led to poor results.

In the 1940s, Whipple and the Columbia Presbyterian group in New York initiated an era of success for portal decompression.3 The next 40 years saw many refinements to decompressive shunts, Drapanas with mesocaval shunts,4 Warren and Inochuchi with selective variceal decompression,5,6 and Sarfeh with partial shunts.7 This era saw many randomized trials documenting efficacy of shunts.

Endoscopic therapy was the next major advance in managing variceal bleeding, being first done by surgeons with rigid esophagoscopes.8 In the 1980s, three surgeons, Johnston, Terblanche,9 and Paquet,10 bridged the gap from rigid to flexible variceal sclerotherapy. Another surgeon, Steigmann,11 moved the field forward by introducing variceal band ligation.

Over the last three decades, the more recent advances have been made by nonsurgeons. A better understanding of the pathophysiology, the ability to better evaluate liver diseases, the introduction of pharmacologic therapy, development of the radiologic shunt, and coming of age of liver transplantation are the main contributors to this progress. Lebrec and his colleagues in the 1980s introduced beta-blockers to reduce portal hypertension,12 and this has become the primary treatment for reducing the risk of an initial variceal bleed and first-line treatment for those who have bled. Transjugular intrahepatic portosystemic shunt (TIPS), pioneered by Rösch,13 has led to shunts being more safely placed by the radiologist than the surgeon with lower early morbidity and mortality.

However, two surgeons, Starzl14 and Calne,15 revolutionized the whole field of hepatology with their persistence in developing liver transplantation through the 1960s to 1980s, and bringing it to a clinical reality. Transplantation has not only offered a treatment for patients with end-stage liver disease and portal hypertension, but has also opened the doors to further investigation.

It is around this history of portal hypertension that many of the investigative and treatment options discussed in this chapter are built.

The pathophysiology of portal hypertension16,17 has been clarified over the past two decades in animal models documenting the sequential changes in the splanchnic and systemic circulations. The sequence of events is as follows:

• Block to portal flow leads to increased portal pressure.
• Splanchnic vascular bed response.

  1. Initial increased vasoconstrictor and decreased vasodilator response increases intrahepatic resistance.

  2. Secondarily, the vasodilator response dominates, with increase in splanchnic inflow.

• Collaterals develop between the portal circulation and the systemic circulation.
• Plasma volume expansion occurs with the development of a systemic hyperdynamic circulation.

The splanchnic vascular response leads to increased flow in the gut and thus major clinical manifestations of collaterals in multiple locations: at the umbilicus, in the retroperitoneum, hemorrhoidal, and at the gastroesophageal junction.

The systemic hemodynamic changes result in cardiac outputs in the 10–15 L/min range, systolic blood pressures in the 100–110 range, and a low calculated total systemic vascular resistance. These changes have significant management implications for fluid resuscitation and patient management. It is important for the managing physician to understand these pathophysiologic changes and their impact on patient care.

The major complications of portal hypertension are as follows:

• Variceal bleeding
• Ascites
• End-stage liver disease
• Hepatopulmonary syndromes

This chapter will address the etiology, evaluation methods, specific therapies, and overall treatment strategies for each of these complications. An important distinction in patients with portal hypertension is between those with ascites and encephalopathy, which are markers of advanced liver disease, and patients with variceal bleeding, which may occur in patients with a normal liver (portal vein thrombosis) or early in the course of cirrhosis. The implication of this is that the range of treatment options is considerably broader for variceal bleeding than it is for patients with ascites and encephalopathy.

Figure 47-1 illustrates the wide range of etiologies for portal hypertension.18 In the United States and Europe, approximately 90% of patients with portal hypertension have cirrhosis, with a small percentage having portal vein thrombosis (PVT) or hepatic fibrosis. The latter are important to differentiate because they have normal liver function and a much better prognosis. Worldwide, schistosomiasis is an important etiology of portal hypertension, occurring mainly in the Middle and Far East and South America. It is characterized by fibrosis of the terminal portal venules, and in the absence of concurrent hepatitis, these patients have normal liver function.

Cirrhosis covers a broad spectrum of disease by etiology and severity. Alcoholic liver disease and hepatitis are the most common etiologies, with other causes, such as the cholestatic liver diseases of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), and the metabolic liver diseases such as hemochromatosis, Wilson's disease, and α1-antitrypsin deficiency, contributing a small percentage. Whatever may be the etiology of the cirrhosis, full evaluation of activity and stage of the disease is an important part of initial patient evaluation. Different etiologies may have different natural histories which is important in developing a treatment plan.

The evaluation of patients with portal hypertension has the following essential components, and should be done at initial presentation:

• Assessment of the liver disease
• Assessment of the portal circulation
• Upper gastrointestinal (GI) endoscopy

Liver evaluation19,20 is based on clinical findings and laboratory studies. Jaundice, ascites, encephalopathy, and malnutrition define a patient with end-stage liver disease. Some patients with variceal bleeding do not show these clinical signs and have well-preserved liver function. Laboratory tests add objectivity, the most useful indicators being serum bilirubin, albumin, prothrombin time, and creatinine. The two main scoring systems for liver disease severity are the Child-Pugh score19 (Table 47-1) and the Model for End-stage Liver Disease (MELD) score20 (Equation 47-1). Specific serologic markers may be useful in defining etiology for viral hepatitis, or for some of the metabolic diseases with antimitochondrial antibody, iron studies, a1-antitrypsin, or ceruloplasmin levels. In addition, alpha-fetoprotein (AFP) should be measured in all such patients as a screening test for hepatoma.

Equation 47-1

MELD Score

Score = 0.957 × loge creatinine (mg/dL) + 0.378 × loge bilirubin (mg/dL) + 1.120 loge INR

When a patient has portal hypertension, usually shown by varices, a cause must be found. If clinical and laboratory studies do not fit, imaging and a liver biopsy may be indicated. Quantitative liver testing with studies such as indocyanine green clearance, galactose elimination capacity, and monoethylglycinexylidide (MEGX) formation are advocated by some, but have not proved to be clinically useful.

Imaging is initially with ultrasound to show overall liver morphology and potentially to pick up focal lesions suggestive of hepatoma. Contrast-enhanced computed tomography (CT) scan or magnetic resonance imaging (MRI) may be required for morphologic assessment. Liver biopsy may be required to confirm that some patients do have underlying cirrhosis, and in cases of focal lesions, to differentiate hepatocellular carcinoma from regenerative nodules. In the latter case a biopsy of the uninvolved liver is performed as well as the focal lesion to assess for cirrhosis.

Vascular anatomy is evaluated with imaging modalities of escalating complexity depending on information required for management.21–23 Doppler ultrasound can assess the hepatic artery, portal and hepatic veins and this may be all that is required. Documenting size, directional flow, velocities, and wave-form patterns of the portal and hepatic veins is a standard procedure. Tributaries to the portal vein—the superior mesenteric and splenic veins, and large collaterals such as the coronary and umbilical vein may also be readily defined. The most important information that the clinician needs to know is the patency (or thrombosis) of the portal vein. Hepatic artery patency, course, and resistive index can be assessed with Doppler ultrasound.

The next level of complexity for evaluating the liver circulation is with CT scan or MRI. These two modalities may be combined with CT or MR angiography (MRA). The speed of scanners, new contrast-enhancing agents, and the increasingly advanced software for data reconstruction allow sophisticated imaging of the liver's arterial and venous anatomy. These methods have improved preoperative planning for living donor liver transplantation and liver resection.

Finally, angiography still plays a role for direct pressure measurement and clarification when the prior modalities are unclear. Portal pressure is measured indirectly from the hepatic veins by measuring wedged and free hepatic vein pressures, with the difference being the hepatic venous pressure gradient (HVPG).24 This is done using a balloon occlusion technique akin to a Swan-Ganz catheter measurement in the pulmonary circulation. Normal HVPG is 6–8 mm Hg, and in cirrhosis it will be greater than 10 mm Hg. There has been resurgence of interest in HPVG to measure response to pharmacologic therapy. Direct portal pressure measurement also can be done by the transjugular, transhepatic route. This method, useful in the acute situation particularly when combined with TIPS, is not used for repeated measurements.

Upper GI endoscopy is used to assess varices. All patients with cirrhosis should have an upper endoscopy. This recommendation is based on epidemiologic studies that have shown the following:

• Thirty percent of patients with cirrhosis develop portal hypertension.
• Thirty percent of patients with portal hypertension will bleed from varices within 2 years.
• The rate of development of varices in patients with cirrhosis is approximately 8% per year.

Endoscopy should focus on the presence of varices; the size, extent, and tortuosity; and the presence or absence of red color signs. Large varices with red color signs are at greater risk of bleeding. In patients with cirrhosis and upper GI bleeding, endoscopy may be both diagnostic and therapeutic with banding. Following an acute variceal bleed, the extent of varices should be assessed after stabilization. Grading systems for varices have been developed and validated by the Japanese25 and Italians.26 Finally, the gastric mucosa should be evaluated for evidence of portal hypertensive gastropathy with congestion and cobble stoning.27 Gastric varices may also be seen, with isolated gastric varices being more problematic than gastric varices in continuity with esophageal varices.28

Figure 47-2 illustrates a management algorithm for variceal bleeding that requires a multidisciplinary team, and may vary from center to center depending on available expertise. The team should have a predetermined, step-wise management plan for patients with variceal bleeding. This algorithm will form the basis for further discussion of patients.

The following therapies are available for treating variceal bleeding:

• Pharmacotherapy
• Endoscopic therapy
• Decompressive shunts—radiologic or surgical
• Devascularization operations
• Liver transplantation

Pharmacologic therapy plays a role in preventing the initial bleed, managing the acute variceal bleed, and as first-line treatment in preventing rebleeding.

Noncardioselective beta-blockers (Inderal [propranolol hydrochloride] or nadolol) were shown by Lebrec and his colleagues in the early 1980s to reduce portal hypertension.12 Patients with moderate- to large-size varices should be placed on one of these drugs for prophylaxis prior to their first bleed. Not all patients tolerate beta-blockers or are responsive to them, with a noncompliance or fallout rate of about 20%. The target for treatment is greater than 20% or less than 12 mm Hg reduction in HVPG. If this is achieved, patients will not bleed.29

Propranolol or nadolol are used as initial therapy to prevent rebleeding, with the same caveats for tolerance, response rates, and targets for therapy. Many other pharmacologic agents have been evaluated such as long-acting nitrates, serotonin antagonists, and calcium channel blockers. None of these have been shown to be as efficacious as the beta-blockers, and while combination therapy has been beneficial in some studies, it has been limited by side effects.29,30

Pharmacologic therapy for acute variceal bleeding was initially with vasopressin. It has been largely replaced by terlipressin, or somatostatin or one of its analogs. These drugs effectively reduce portal pressure in the patient with acute variceal bleeding.

Endoscopic Therapy

The current standard for endoscopic therapy for esophageal varices is endoscopic banding.11 This has largely replaced endoscopic sclerotherapy because it has fewer side effects, obliterates varices faster, and can be easily applied. Multiband ligators can be fitted on the end of the endoscope and allow the firing of six to eight bands in a spiral fashion onto columns of varices. The varix is sucked into the end of the applicator, and the band fired around its base. The bands will slough off in 5–7 days with less ulceration over the varices than induced by sclerotherapy, and hence a lower initial rebleeding rate. Endoscopic banding can be used in the patient with acute variceal bleeding if the bleeding varix can be identified. A course of banding—usually two to three sessions—is then applied over the next month to 6 weeks in an attempt to obliterate the varices at the gastroesophageal junction. Occasionally, endoscopic sclerotherapy with injection of a sclerosing solution may be a useful adjunct to complete the obliteration of smaller varices that cannot be banded.

Many prospective, randomized controlled trials have documented better control of bleeding with endoscopic banding than sclerotherapy, with lower morbidity. However, the mortality was not significantly different between banded and sclerosed patients in these trials.31

From a practical point of view, patients with an acute variceal bleed should have their bleeding controlled with an endoscopic session, have their varices obliterated with a course of banding, and be placed on a noncardioselective beta-blocker for long-term management. This constitutes first-line treatment.

Decompressive Shunts

This component of management of variceal bleeding has changed dramatically over the last two decades. Decompression is considered second-line treatment and is reserved for patients who rebleed through pharmacologic therapy and endoscopic banding or whose varices remain “high risk.” Very few surgical shunts are performed at the current time, and patients requiring decompression are usually managed with a radiologically placed shunt—TIPS.

Surgical shunts are largely of historic interest and fall into three groups: total, partial, and selective shunts.

Total Shunts

Figures 47-3 and 47-4 illustrate total shunts,32,33 with two physiologically different types. Figure 47-3 shows a classic end-to-side portacaval shunt in which the portal vein is divided close to the hilus of the liver and the splanchnic end anastomosed to the side of the vena cava. This decompresses the splanchnic portal hypertension but leaves the obstructed sinusoids under high pressure. As such, it will not relieve ascites but will control variceal bleeding.

Figure 47-4 illustrates the second group of total shunts, which are either side-to-side portacaval shunts with direct vein-to-vein or a short interposition graft, or the other interposition shunts such as mesocaval or mesorenal as illustrated. These shunts need to be at least 10 mm in diameter, usually being 12–15 mm, to fully decompress portal hypertension and be classified as a total shunt. Pathophysiologically, these shunts differ from the end-to-side portacaval shunt in that the intact upper end of the portal vein serves as a decompressive outflow from the high-pressure–obstructed liver sinusoids. Hence, in addition to controlling variceal bleeding, these shunts also control ascites.

These total shunts (>10 mm in diameter) divert all portal flow away from the liver and the major debate has been the effect that this has on hepatic function. Data are conflicting as to the severity of the portoprival syndrome (diversion of all portal flow), its effect on liver function, and its role in causing encephalopathy. It is almost certainly the severity of the underlying liver disease, which is the dominant factor in whether a shunt accelerated liver failure.

The technical aspects of a side-to-side portacaval shunt are relatively straightforward. The portal vein and inferior vena cava are approached from the right side, usually through a long right subcostal incision. Sufficient length of the portal vein is mobilized in the right edge of the hepatoduodenal ligament. The inferior vena cava is mobilized from the lower border of the liver to the renal veins. This will usually allow for a direct side-to-side portacaval anastomosis. When the caudate lobe is particularly large, either a segment of this may be excised, or a short interposition graft may be used. These vessels are familiar territory to the transplant surgeon, who can perform this operation in the few patients in whom it is indicated.

The only indication for a total portal systemic shunt at present is for patients with acute Budd-Chiari syndrome in which the congested intrahepatic sinusoids need to be decompressed using a side-to-side total shunt.34

Partial Shunts

Partial shunts are side-to-side shunts whose diameter is reduced to 8 mm. Sarfeh and associates in the 1980s systematically reduced the size of polytetrafluoroethylene (PTFE) interposition grafts between the portal vein and the inferior vena cava down to 8 mm diameter, showing that at this size there is a greater than 90% control of variceal bleeding and maintained portal perfusion in 80% of patients.7 This shunt has been used in a randomized trial compared to TIPS.35,36 The surgical approach is similar to that used for a side-to-side portacaval shunt, with the PTFE graft being approximately 2–3 cm long, and beveled at each end to give a larger anastomosis.

Selective Shunts

Selective shunts are most commonly the distal splenorenal shunt (DSRS) (Fig 47-5).5 This shunt leaves the spleen in situ, divides the splenic vein at its junction with the superior mesenteric vein, and anastomoses the splenic vein to the left renal vein. This selectively decompresses gastroesophageal varices. Portal hypertension is maintained in the splanchnic and portal veins to maintain portal flow to the liver in Child's class A and B+ patients. Control of bleeding has been at 94%, with good portal perfusion maintained in 90% of patients initially. Portal flow is preserved in greater than 90% of patients with nonalcoholic liver disease long term, but loss of portal flow occurs in 50% of alcoholic patients. The overall incidence of encephalopathy has been around 15% following this operation.37–41

DSRS is done through a long left subcostal incision. The pancreas is approached through the lesser sac, taking down the gastrocolic omentum to the short gastric vessels, and the splenic flexure of the colon. The pancreas is then mobilized along its inferior margin over it whole length to the left of the superior mesenteric vessels. The splenic vein is identified and carefully dissected out from the posterior surface of the pancreas over sufficient length to allow it to come down to the left renal vein without kinking. The operation is completed by interrupting the other collateral pathways between the portal vein and the shunt, particularly the coronary vein.

Postoperative management for all of these surgical procedures requires attention to detail. Patients should be managed in a monitored environment for 24 hours to make sure they are hemodynamically stable and there is no early postoperative bleeding. Limiting intravenous (IV) fluids and sodium helps minimize the risk of ascites. Infection prophylaxis, nutrition, and careful monitoring of hepatic function are important. Shunt patency should be documented prior to hospital discharge with imaging studies.

Transjugular Intrahepatic Portal Systemic Shunt

TIPS has matured over the last two decades, and is now the most widely used method for decompressing portal hypertension in patients with variceal bleeding or ascites.42–44 It is an important part of the repertoire for the multidisciplinary team managing these patients. Figure 47-6 shows the principles of TIPS. The technical approach to TIPS is direct puncture of the internal jugular vein (IJV), passage of a catheter through the right atrium into one of the major hepatic veins—usually the right vein—followed by a transparenchymal puncture of the liver to cannulate the portal vein. The catheter is passed into the portal vein and pressure is measured. The portal vein puncture may be aided by ultrasound definition of its location. The intraparenchymal track is then dilated and the track stented with an expandable metal stent in the 10- to 12-mm-diameter range. Pressures are again measured and the goal is to decrease the gradient between the portal vein and the right atrium to less than 10 mm Hg. The technical success rate is high (>90%) with a low procedural morbidity and mortality (<10%). Patients are usually in the hospital for 1–2 days and the shunt patency should be documented the day after the procedure with a Doppler ultrasound.

The major issue with TIPS is its restenosis and thrombosis rates, which requires careful monitoring, and dilation and/or shunt extension when detected. The risk of early thrombosis seems to be related to bile duct puncture as the parenchymal track is developed. Covered TIPS stents have reduced thrombosis and stenosis rates. While a Doppler ultrasound will document patency, it has not proved to be a sensitive method for documenting stenoses, which requires direct measurement of the pressure gradient. Reintervention rates to maintain patency were high with uncovered stents, ranging from 40 to 80%, but have fallen to about 20% with covered stents.45 The overall published rebleeding rates for TIPS are around 20%, and this was reduced to 13% in the covered stent trial.45 Most centers have developed standard follow-up protocols to monitor TIPS, which call for repeated Doppler ultrasound. New encephalopathy rates are around 30%. Most of this encephalopathy appears to be relatively easily controlled with lactulose and/or some minimal protein restriction.

Devascularization Procedures

These operations approach the problem of variceal bleeding by interrupting inflow to the varices. The components are splenectomy, gastric and esophageal devascularization, and possibly esophageal transaction (Fig. 47-7).46 The effectiveness of these procedures appears to depend on the aggressiveness of the operation. Popularized by Sugiura in Japan46 and Hassab in Egypt, good results have been obtained in these countries. The advantage of these procedures is that portal hypertension is maintained with portal flow to the cirrhotic liver. Control of variceal bleeding in the originators' hands has been greater than 90%,47 but higher rebleeding rates (~30%) have been seen in Europe and the United States.48 These results are probably related to applying this operation to poorer-risk patients who are not candidates for other operations and inadequate operative devascularization. More recent application of devascularization procedures by Orozco and colleagues in Mexico has achieved good results with a 10% rebleeding rate.49

From a technical perspective, the original Sugiura operation combined an abdominal and a thoracic procedure either as a single- or two-stage approach. More recently, most surgeons have approached devascularizations purely from an abdominal approach. Standard devascularization operations include splenectomy, but Orozco and colleagues have published data indicating this is not essential. The whole of the greater curve should be devascularized, at least 7 cm of the distal esophagus, and finally the upper two-thirds of the lesser curve of the stomach. Attempts are made to keep the vagus nerve intact and the devascularization has the appearances of a proximal gastric vagotomy as the operation is completed. Because many of these patients have received sclerotherapy or banding prior to operative intervention, most do not need an esophageal transection, which can be difficult with the thickened esophagus.

Devascularization can be useful when patients have extensive portal and splenic venous thrombosis and there are no other operative or radiologic options. Extensive devascularization will reduce the risk of bleeding in such patients, and this remains the main indication for this operation.

Postoperative management requires attention to detail to minimize the risk of ascites as these patients still have portal hypertension. Follow-up endoscopy around 6 months is often helpful to document if there are any residual varices, treat them endoscopically at that time, or document the completeness of the devascularization procedure.

Overall, the bleeding rates can be reduced to less than 20% with this procedure and encephalopathy rates are low.

Liver Transplant

Liver transplant is the most commonly used operation for patients with portal hypertension at the present time,50–52 and has been the major advance in the treatment of patients with advanced liver disease and sequelae of portal hypertension. The major issues are patient selection, timing of transplant, expanding the donor pool, and outcomes.

Patient selection has evolved over the past two decades. The indication for transplant is end-stage liver disease, but definition of this in the field of hepatology is a moving target. Variceal bleeding per se is not necessarily an indication of end-stage liver disease but other manifestations of portal hypertension such as ascites and encephalopathy are clinical indicators of end-stage liver disease. Patient selection also depends on other variables such as comorbid medical conditions and a psychosocial suitability for transplant particularly in the alcoholic and other chemical dependency patient populations. The increase in the incidence of hepatoma, particularly in the hepatitis C population, has also changed indications for patient selection for liver transplant. Standards for patient listing have been set by the United Network for Organ Sharing (UNOS), with evolving indications proposed by individual liver centers considered by regional review boards.

The timing of transplant is dictated by the severity of the underlying liver disease. Prioritization for organs occurs on the basis of MELD scores, with the sickest patients receiving cadaveric organs first based on bilirubin, prothrombin time, and serum creatinine. Timing is dictated by these objective criteria rather than individual physician decisions in day-to-day patient management. The donor pool for liver transplant has expanded with increasing public awareness of the need for organ donation, the use of “expanded donor” criteria with concomitant documentation that these organs do work, and the application of living donor transplant. The direct impact of these changes on the donor pool, the systems of organ allocation and prioritization, and individual center philosophies and priorities for their patients have changed and will continue to change the role of liver transplantation in portal hypertension.

The outcomes with liver transplant have continued to improve. The fear that pushing organs to the sickest patients would lead to poorer outcomes has not been fulfilled. Hospital mortality remains at less than 10%, despite transplanting in sicker and sicker patients and despite using more marginal organs. This is testimony to the advances in the fields of organ preservation and overall patient management during and following liver transplantation. The expectation therefore for outcomes is less than 10% hospital mortality and an 80+% 1-year survival with a 60–65% 5-year survival for liver transplant.

Technical aspects of liver transplant have focused on use of whole organ grafts, partial segmental grafts, living donor grafts, techniques of caval preservation, alternative methods of revascularization, and improved methods for biliary reconstruction. In addition to these technical advances in the transplant field itself, the increasing number of surgeons who have developed this expertise also represent the pool of surgeons with the ability to conduct some of the operative procedures described earlier in this chapter.

The management and longer-term follow-up of patients with portal hypertension coming to liver transplant is likewise an evolving field. Improvement in methods of immunosuppression, infection prophylaxis and treatment, patient monitoring to reduce the risk of transplant-related malignancy, and long-term health maintenance after transplant are ongoing fields of investigation and improvement. The net result of all of these advances is that patients with Child's class C cirrhosis, variceal bleeding, and advanced liver disease can now look forward to a reasonable chance of long-term survival, whereas 15–20 years ago, they had a 15–20% chance of long-term survival.

Variceal Bleeding

The treatment options just described need to be used appropriately in treatment strategies for

• Prophylaxis
• Acute variceal bleeding
• Prevention of rebleeding

Prophylaxis

Beta-blockers should be used for all patients with medium or large varices to reduce their risk of an initial bleed. Bleeding risk can be reduced from 30% to 18–20% with beta-blocker treatment. Multiple randomized controlled trials have documented this benefit. Patients with cirrhosis should have a screening endoscopy to assess for varices and initiate treatment if appropriate.29,30

Endoscopic therapy for prophylaxis should only be used for large varices and patients intolerant to beta-blockers.53 Surgical therapy or radiologic shunts are not indicated in prophylaxis prior to an initial variceal bleed.30

Acute Variceal Bleeding

Acute variceal bleeding may require several treatment modalities and outcome has improved in the past decade.54 Most important is the overall management of the patient rather than the specific therapies. Airway protection, appropriate fluid resuscitation, adequate monitoring, and antibiotic prophylaxis are all now standard of care for such patients. Transfusion of blood for bleeding, blood products for coagulopathy must be carefully monitored with a target of under- rather than over-resuscitation. Pharmacologic therapy with intravenous octreotide (50 μg/h) will reduce portal pressure and should be initiated on suspicion of a variceal bleed. Early endoscopy, both for diagnosis and initial banding therapy, is the mainstay of treatment.55 Endoscopic banding can be done provided the varix is visualized and can be sucked into the end of the scope. In the occasional patient in whom endoscopic therapy cannot be performed, balloon tamponade should be used to control bleeding. Inflation of the gastric balloon alone, pulled gently up into the gastric fundus, will usually suffice to control bleeding. If that fails to control the bleeding, the esophageal balloon may need to be inflated to 40 mm Hg. Placement of a tamponade balloon mandates further reintervention within 24 hours, and this is usually an indication for an emergency TIPS procedure.

TIPS is required in fewer than 10% of patients with acute variceal bleeding.42 Emergency TIPS placement needs to be treated in the same way as if the patient were going to the operating room. Airway protection, careful monitoring, and appropriate fluid management and resuscitation are required. While the radiologist is concentrating on the technical aspects of placing an accurate decompressing TIPS shunt, the patient overall management team needs to assure all other aspects of care are completed.

The patient with an acute variceal bleeding episode still carries a significant mortality risk, death most commonly resulting from decompensation of the underlying liver disease. A major bleed requires an intensive care unit (ICU) admission, but once stable, patients can be transferred to a regular hospital floor. Early evaluation and follow-up endoscopy to initiate an elective course of banding is the next step in overall patient management.

Prevention of Rebleeding

The first-line treatment for prevention of rebleeding is a course of variceal banding and concomitant pharmacologic therapy with a beta-blocker no matter what the underlying cause is.29,30 The first elective banding episode should be performed within 3 or 4 days of the acute bleeding episode and as many bands placed as necessary to obliterate the columns of varices in the distal esophagus. Subsequently one or two banding sessions will probably be required to obliterate these varices. A beta-blocker is started with the target of reducing the pulse rate by 20% and with the plan to use this for long-term therapy.

Overall patient care also mandates a full evaluation of the patient at this point.56,57 An understanding of the etiology of the liver disease, its severity, its likely natural history, and looking for other complications of portal hypertension should be completed at this stage. Several possible case scenarios may emerge:

• Good-risk patients—Child's A patients or MELD less than 10. Patients who still look like a Child's A patient after a variceal bleed and have MELD scores less than 10 probably have well-compensated liver disease. These patients should be treated with first-line treatment, but if they rebleed or have failure to obliterate their varices with banding, they may be a candidate for decompression with TIPS or DSRS.
• Indeterminate patients—Child's B or MELD 10–16. The majority of patients will fall into this category after their variceal bleed with some disturbance in their liver laboratory numbers, possibly developing ascites, and having an unpredictable course for their liver disease. From a management perspective, the question is whether these patients will improve to Child's A, remain Child's B patients, or move toward end-stage disease. Their initial treatment is with endoscopic banding and a beta-blocker. Subsequent treatment depends on the course of their liver disease.
• End-stage liver disease—Child's C or MELD greater than 16. If initial evaluation shows Child's C cirrhosis and patients clearly are not improving with routine clinical management, consideration needs to be given to full transplant evaluation. The severity of the bleeding episode may play some role in whether or not these patients' disease will return to a compensated level or whether they will continue to deteriorate secondary to the acute bleeding episode.

Failure of first-line treatment can occur in several scenarios. The main reasons are (1) the patient may have a further acute variceal bleed, (2) the patient may have recurring small bleeding episodes that are not transfusion-requiring, or (3) the patient may fail to have the varices obliterated and continue to have large varices with risk factors. Patients with any of the above scenarios, who also have advanced liver disease, are candidates for liver transplantation, possibly using TIPS as a bridge. Any of the above occurring in patients with well-compensated liver disease (Child's class A) may lead to variceal decompression with DSRS or TIPS.

Decompression with TIPS versus a surgical shunt has been evaluated in two randomized controlled trials. Rosemurgy and associates36 studied the relative benefits of TIPS versus the 8-mm portacaval H-graft shunt. In their “all comers” study of 132 patients, 50% of their population were Child's class C patients. They showed a significantly lower rebleeding rate, and significantly lower rate of need for transplant with the surgical shunt compared to the TIPS group, but no significant difference in survival.

A randomized trial compared DSRS to TIPS at five clinical centers in 140 Child's class A and B patients who failed first-line treatment.58 Data showed no significant difference in rebleeding rates (5.5% DSRS group, 10.5% TIPS group), no significant difference in the times to first encephalopathy episode with 50% of patients in each group having at least one episode of encephalopathy by 5 years, and no significant difference in survival between the two groups. However, the reintervention rate in the TIPS group was significantly (p < .001) higher at 82% compared to a reintervention rate of 11% in the DSRS group. The rate of total thrombosis was significantly higher in the TIPS group compared to the DSRS group. This study used uncovered TIPS stents, which was all that was available at the time of this National Institutes of Health (NIH)-funded trail. The excellent results were achieved through intensive surveillance in the TIPS group compared to the DSRS patients to achieve the low rebleeding rate. A cost-effectiveness analysis of patients in this trial showed TIPS may be more cost-effective than DSRS in good risk Child's AB patients.59

Studies of TIPS with covered stents have shown significant advantages compared to uncovered stents for rates of stenosis and rebleeding.60 This has now become the standard for variceal decompression when needed.

Ascites

The management of ascites is primarily medical with dietary salt restriction and diuretics (spironolactone and furosemide).61 When ascites becomes refractory to such a regimen, large-volume paracentesis or TIPS may be considered, but these are a bridge to transplant. As indicated above, refractory ascites is one of the major clinical signs of end-stage liver disease. Four randomized trials have shown benefit and better control of ascites with TIPS compared to large-volume paracentesis, but survival benefit was only shown in two of four studies.62–65

Other surgical methods that have been used to manage ascites are side-to-side total portal systemic shunts and peritoneovenous shunts. The only indication currently to use a side-to-side (>10 mm) portacaval shunt for ascites is in patients with acute Budd-Chiari syndrome in whom decompression of the liver sinusoids with this operation will not only relieve their ascites, but will also stop the centrilobular hepatocyte necrosis and allow the liver to recover. The question to be answered in such a patient with acute Budd-Chiari syndrome is whether the same result can be achieved with TIPS.

Peritoneovenous shunts are seldom indicated in 2010 because the alternatives for managing intractable ascites, large-volume paracentesis, TIPS, and liver transplant are more satisfactory. Peritoneovenous shunts, with either a pressure-activated or a patient-activated pumping valve, were introduced in the 1970s and proved to be effective in the short term, but have largely been abandoned because of complications. Occlusion occurs in over half by 6 months, disseminated intravascular coagulation is triggered by reinfusion of ascites, and infection is a significant risk in this susceptible population.66 Patients with complications from their intractable ascites, such as leakage at an umbilical hernia, are best managed with repeated paracentesis and/or TIPS.

The surgeon's role in treating patients with ascites is now limited to liver transplant which is the best therapy for patients with intractable ascites. The issue is candidacy for and availability of transplant.

Lung dysfunction has been recognized in some patients with liver disease and portal hypertension for more than a century, but it is only in the last two decades that two distinct pulmonary vascular disorders have been better understood.67,68 Hepatopulmonary syndrome (HPS) occurs when there is a pulmonary vascular vasodilation and hypoxemia, whereas portopulmonary hypertension (PPH) occurs when there is pulmonary vasoconstriction and increased pulmonary artery pressure. The major features of these two syndromes are summarized in Table 47-2.

The comparative contributions of liver dysfunction and portal hypertension vary with these syndromes. HPS can occur without severe portal hypertension and has also been recognized in some patients with prehepatic and postsinusoidal blocks. PPH can occur when the degree of liver dysfunction is relatively minor in the presence of established portal hypertension.

Shortness of breath is the most common presentation for either HPS or PPH.69–72 Increased dyspnea on standing, cyanosis, and finger clubbing are often present with HPS and should lead to evaluation for this syndrome in patients with cirrhosis. Although patients with PPH may present with dyspnea, they are more likely to be asymptomatic. It is important to differentiate these pulmonary syndromes because treatment is different.

In HPS, diagnosis is made on patients hypoxemic on room air (PO2 <70 mm Hg) by a bubble-contrast echocardiogram.73 If this is positive as judged by delayed visualization of intravenously administered microbubbles in the left cardiac chamber, the patient has HPS. Patients with HPS require oxygen therapy, but the only effective treatment for HPS is liver transplant.

The diagnosis of PPH requires documentation of elevated pulmonary arterial pressures.74 Echocardiography is used for screening for elevated right heart pressure,75 but when the estimate is equal to or greater than 40 mm Hg, direct pulmonary artery pressure measurements should be made with right heart catheterization. A mean pulmonary artery pressure of greater than 25 mm Hg with a capillary wedge pressure of less than 15 mm Hg confirms a diagnosis of pulmonary arterial hypertension. Mild degrees of pulmonary arterial hypertension up to 35 mm Hg do not preclude liver transplantation in otherwise acceptable candidates, but pressures greater than 35 mm Hg require aggressive evaluation and treatment. Pulmonary artery pressures greater than 50 mm Hg are an absolute contraindication to liver transplantation.76 Patients with pulmonary artery pressure greater than 35 mm Hg should receive pharmacologic therapy, with reassessment after 3 months.77 Response to this treatment may make such patients candidates for liver transplantation.

The content of this chapter has involved many specialists to take care of the complications of portal hypertension, including the following:

Hepatologists are in the front line for diagnosing and directing the management for many of the clinical presentations.

Endoscopists play an important role diagnostically and in primary therapy for managing variceal bleeding. Endoscopic banding requires significant expertise.

Radiologists, both imaging and interventional, play roles in diagnosis, directed biopsy, and procedural (TIPS) management of these patients.

Surgeons play a major role in liver transplant but may also have a role in shunting good-risk patients with refractory variceal bleeding.

Pathologists with an interest in liver pathology are important in the accurate diagnosis and staging of disease severity.

Critical care physicians and anesthesiologists are vital team members when patients with portal hypertension have acute events and in their perioperative management. The different pathophysiology of portal hypertension can be challenging in the ICU and operating room.

Nephrologists, cardiologists, and pulmonologists all play a role in the management of some of these patients, and in major centers it is important to have members of all these specialties in the team who understand the pathophysiologic changes of portal hypertension.

Finally, who coordinates? In a complex multidisciplinary team such as described, it is frequently the nurse clinicians or coordinators who help bring these specialists together. Undoubtedly the coordinators are the ones to whom the patients turn for help in navigating their way through management in this complex field.