Alcoholic liver cirrhosis

The management of patients with esophageal varices requires an integrated approach that incorporates pharmacotherapy, endoscopy, transjugular intrahepatic portosystemic shunts (TIPS) and surgery. Propranolol (Inderal) therapy is the mainstay in preventing the initial variceal hemorrhage and recurrent bleeding. Endoscopic sclerotherapy or ligation and stapled esophageal transection are localized treatments for esophageal varices. Surgical shunts and TIPS reduce variceal pressure by decreasing the portal pressure. Only liver transplantation resolves the underlying problem. Selection of the appropriate intervention is dependent on the patient's hepatocellular function, response to treatment and coexisting conditions.

Liver disease is one of the 10 leading causes of death in the United States, and at least 40 percent of cases are related to alcohol abuse. Alcoholic cirrhosis is the most frequent cause of portal hypertension, which leads to esophageal varices. Approximately one third of patients with cirrhosis have bleeding from esophageal varices, a complication that accounts for nearly 30 percent of deaths among cirrhotic patients. Since more than 10 million Americans abuse alcohol, cirrhosis and bleeding esophageal varices remain a significant health problem.

Etiology

Alcoholic cirrhosis may be complicated by ascites, coagulopathy, renal failure, hypoxemia, encephalopathy and esophageal varices secondary to portal hypertension. Table 1 lists clinical findings that may be encountered in a patient with cirrhosis who has portal hypertension. TABLE 1 Clinical Findings Associated with Cirrhotic Liver Disease

Sclerotherapy is considered a failure when bleeding persists after two treatments in 24 hours. In this situation, balloon tamponade, esophageal transection, a surgical shunt and the TIPS procedure are considered. Some authors recommend stapled esophageal transection as the procedure of choice in this setting (Figure 3).[18] It is technically easier to perform than a shunt and has a lower operative mortality, but the likelihood of rebleeding is greater. In addition, stapled transection is ineffective in the presence of portal hypertensive gastropathy. Shunts, however, are associated with an operative mortality rate as high as 50 percent, despite their efficacy in curtailing hemorrhage.[19]

The use of TIPS has two well-defined indications.[20] It can be employed as a salvage procedure or as a bridge to liver transplantation. The salvage procedure is used in Child's class C patients with acute variceal bleeding that cannot be controlled either medically or with sclerotherapy.[21] These patients have a very high operative mortality rate. The TIPS technique avoids the adverse effects of general anesthesia on hepatocellular function, since the shunt can be inserted in the radiology suite using local anesthetics (Figure 4).[22]

The most accepted indication for TIPS is its use as a bridge to transplantation. The procedure entails the formation of a type of portosystemic shunt as a stent is placed in the hepatic parenchyma to create a connection between an intrahepatic branch of the portal vein and a hepatic vein. TIPS shares many of the attributes and disadvantages of surgical portosystemic shunts. Both interventions control variceal bleeding and alleviate refractory ascites.[23] However, these short-term benefits are offset by a tendency toward shunt occlusion and encephalopathy. Neointimal hyperplasia accounts for a 50 to 60 percent incidence of shunt stenosis within six months.[22] TIPS does not impair the operative field for patients who are candidates for liver transplantation. Recent studies suggest that TIPS is more effective than endoscopic sclerotherapy in preventing variceal rebleeding in patients with cirrhosis, although no difference in survival was observed.[24]

Balloon tamponade was once an integral element of the management of acute variceal hemorrhage. However, this procedure has many complications, and 60 percent of patients rebleed after balloon removal. The current role of this procedure is to provide a temporizing measure en route to the operating room or the radiology suite.[4]

PREVENTING RECURRENT BLEEDING

Seventy percent of patients with cirrhosis and varices have massive rebleeding within one year of their first hemorrhage.[3] Each hemorrhagic episode carries a 30 to 40 percent mortality rate.[22] The current view is that any intervention undertaken in an elective setting will incur less mortality and morbidity than a comparable procedure performed on an emergent basis.

Propranolol and sclerotherapy have remained the mainstays of long-term management following a variceal hemorrhage. Propranolol therapy may be restarted three to five days after bleeding has ceased and the patient's condition has stabilized. Since sclerotherapy is a localized treatment that does not alter the underlying portal dynamics, patients who undergo this procedure remain at risk for recurrent bleeding. Endoscopic ligation and stapled esophageal transection are also forms of localized treatment that do not prevent the eventual recurrence of bleeding. A recent study[17] favored ligation over sclerotherapy as the endoscopic treatment of choice, based on rates of rebleeding, mortality and complications, as well as the need for fewer endoscopic treatments.

Patients who fail to benefit from sclerotherapy and yet have reasonably good liver function, as evidenced by a Child's A or B classification, are considered good candidates for a surgical shunt[25] (Figure 5). Complete portacaval shunts are 90 to 95 percent effective in preventing recurrent bleeding, but they precipitate liver failure and encephalopathy, with no survival advantage. A group of investigators looked into the use of selective shunts that would decompress esophageal varices while still maintaining a degree of portal hypertension to permit adequate perfusion of the liver. This type of shunt was not found to be effective in alcoholic patients, because they subsequently developed transpancreatic collateral vessels that circumvented the intent of the shunt.[26]

At present, the partial surgical shunt is considered the most effective shunt for the alcoholic patient with cirrhosis.[27] This reduced-caliber shunt will not impair the operative field if a subsequent decision is made to undertake liver transplantation.

Liver transplantation is the treatment option that offers the best survival rates. The major mortality associated with the procedure occurs in the first year. The reported survival rate of patients receiving liver transplants because of variceal hemorrhage is 79 percent at one year and 71 percent at five years.[25] The greatest survival advantage is conferred on the patient who falls in the Child's C class.

One study[28] evaluated survival of patients with cirrhosis who were in Child's C class and were managed with liver transplants, shunts or sclerotherapy After four years, 73 percent of the transplant recipients were alive. This figure stands in distinct contrast to the survival rates in those treated with shunts (31 percent) or with sclerotherapy (59 percent). Clearly, liver transplantation offers the best survival rate as well as improvement in the quality of life. This option, however, is limited by the scarcity of donor organs and the high cost of the procedure.

REFERENCES

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[2.] Boyer TD. Portal hypertension and its complications: bleeding esophageal varices, ascites, and spontaneous bacterial peritonitis. In: Zakim D, Boyer TD, eds. Hepatology: a textbook of liver disease. Philadelphia: Saunders, 1982:464-99.

[3.] Grose RD, Hayes PC. Review article: the pathophysiology and pharmacological treatment of portal hypertension. Aliment Pharmacol Ther 1992; 6:521-40.

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[7.] Prophylactic sclerotherapy for esophageal varices in men with alcoholic liver disease. A randomized, single-blind, multicenter clinical trial. The Veterans Affairs Cooperative Variceal Sclerotherapy Group. N Engl J Med 1991;324:1779-84.

[8.] Prophylaxis of first hemorrhage from esophageal varices by sclerotherapy, propranolol or both in cirrhotic patients: a randomized multicenter trial. The PROVA Study Group. Hepatology 1991;14:1016-24.

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[11.] Andreani T, Poupon RE, Balkau BJ, Trinchet JC, Grange JD, Peigney N, et al. Preventive therapy of first gastrointestinal bleeding in patients with cirrhosis: results of a controlled trial comparing propranolol, endoscopic sclerotherapy and placebo. Hepatology 1990;12:1413-9.

[12.] Conn HO, Grace ND, Bosch J, Groszmann RJ, Rodes J, Wright SC, et al. Propranolol in the prevention of the first hemorrhage from esophagogastric varices: a multicenter, randomized clinical trial. Hepatology 1991;13:902-12.

[13.] Feu F, Bordas JM, Garcia-Pagan JC, Bosch J, Rodes J. Double-blind investigation of the effects of propranolol and placebo on the pressure of esophageal varices in patients with portal hypertension. Hepatology 1991;13:917-22.

[14.] Feu F, Bordas JM, Luca A, Garcia-Pagan JC, Escorsell A, Bosch J, et al. Reduction of variceal pressure by propranolol: comparison of the effects on portal pressure and azygos blood flow in patients with cirrhosis. Hepatology 1993;18:1082-9.

[15.] Sung JJ, Chung SC, Yung MY, Lai CW, Lau JY, Lee YT, et al. Prospective randomized study of effect of octreotide on rebleeding from esophageal varices after endoscopic ligation. Lancet 1995;336:1666-9.

[16.] Stiegmann GV, Goff JS, Michaletz-Onody PA, Korula J, Lieberman D, Saeed ZA, et al. Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med 1992;326:1527-32.

[17.] Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis. Ann Intern Med 1995;123:280-7.

[18.] Burroughs AK, Hamilton G, Phillips A, Mezzanotte G, McIntyre N, Hobbs KE. A comparison of sclerotherapy with staple transection of the esophagus for the emergency control of bleeding from esophageal varices. N Engl J Med 1989;321:857-62.

[19.] Orloff MJ, Bell RH Jr, Orloff MS, Hardison WG, Greenburg AG. Prospective randomized trial of emergency portacaval shunt and emergency medical therapy in unselected cirrhotic patients with bleeding varices. Hepatology 1994;20(4 Pt 1):863-72.

[20.] Shiffman ML, Jeffers L, Hoofnagle JH, Tralka TS. The role of transjugular intrahepatic portosystemic shunt for treatment of portal hypertension and its complications: a conference sponsored by the National Digestive Diseases Advisory Board. Hepatology 1995;22:1591-7.

[21.] Rossle M, Haag K, Ochs A, Sellinger M, Noldge G, Perarnau JM, et al. The transjugular intrahepatic portosystemic stent-shunt procedure for variceal bleeding. N Engl J Med 1994;330:165-71.

[22.] Sanyal AJ, Freedman AM, Luketic VA, Purdum PP, Shiffman ML, Tisnado J, et al. Transjugular intrahepatic portosystemic shunts for patients with active variceal hemorrhage unresponsive to sclerotherapy. Gastroenterology 1996;111:138-46.

[23.] Skeens J, Semba C, Dake M. Transjugular intrahepatic portosystemic shunts. Annu Rev Med 1995;46:95-102.

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[25.] Millikan WJ Jr, Henderson JM, Galloway JR, Dodson TF, Shires GT 3d, Stewart M. Surgical rescue for failures of cirrhotic sclerotherapy. Am J Surg 1990;160:117-21.

[26.] Sarfeh IJ, Rypins EB. Partial versus total portacaval shunt in alcoholic cirrhosis. Results of a prospective, randomized clinical trial. Ann Surg 1994;219:353-61.

[27.] Cabrera J, Maynar M, Granados R, Gorriz E, Reyes R, Pulido-Duque JM, et al. Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage. Gastroenterology 1996;110:832-9.

[28.] Bismuth H, Adam R, Mathur S, Sherlock D. Options for elective treatment of portal hypertension in cirrhotic patients in the transplantation era. Am J Surg 1990;160:105-10.

The Authors

JEANINE TREVILLYAN, M.D. is a second-year resident in the family practice program at the University of Arkansas for Medical Sciences Area Health Education Center (AHEC)-South Arkansas, El Dorado. Dr. Trevillyan is a graduate of UTESA, Dominican Republic.

PETER J. CARROLL, M.D. is the director of the Family Practice Center at the University of Arkansas for Medical Sciences AHEC-South Arkansas. Dr. Carroll attended medical school at Louisiana State University School of Medicine, New Orleans.

Address correspondence to Jeanine Trevillyan, M.D., University of Arkansas for Medical Science AHEC-South Arkansas, 460 West Oak, El Dorado, AR 71730-4587.

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