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:
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.
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.
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.
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.
End-to-side portacaval shunt. This shunt decompresses varices and the splanchnic circulation. Sinusoidal pressure remains high in the cirrhotic liver.
Side-to-side portal systemic shunts. Portacaval, mesocaval, and mesorenal shunts are shown. The portal vein acts as an outflow from obstructed sinusoids, decompressing the liver as well as varices and the splanchnic circulation.
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 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 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
Distal splenorenal shunt (DSRS). Varices are decompressed transplenic to the left renal vein. Portal hypertension is maintained in the splanchnic bed to keep prograde portal flow to the liver.
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.
Transjugular intrahepatic portal systemic shunt (TIPS). This side-to-side shunt has variable hemodynamic effect depending on its diameter.
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.
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
Gastroesophageal devascularization for variceal bleeding. Splenectomy, gastric and esophageal devascularization, and esophageal transection are the components of these operations.
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 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.