Pulmonary hypertension associated with postoperative biliary atresia: Report of two cases

Pulmonary By

Hideki Sotaro

Hypertension Biliary Atresia: Soh,

Toshimichi Mushiake,

Associated With Postoperative Report of Two Cases

Hasegawa, Shigeto

Takashi

Kogaki,

Toru

Sasaki,

Tatsuo

Matsushita,

Azuma,

and

Tokuzo

Akira

Okada,

Harada

Osaka, Japan

The authors report on 2 patients with biliary atresia in whom pulmonary hypertension (PH) developed in the long-term follow-up after hepatoportoenterostomy. Both had portal hypertension and had undergone distal splenorenal shunt. Dyspnea developed around 14 to 15 years of age. Cardiac catheterization showed pulmonary artery pressure (PAP) of 99/37 (58) and 67/32 (48) mm Hg, respectively, which did not respond to vasodilators. One patient suffered from respiratory tract infection followed by right heart failure and subsequent death at 20 years of age. Postmortum histological findings exhibited severe thickening of the pulmonary artery

wall. PH may grow insidiously even after successful hepatoportoenterostomy. Careful monitoring of PAP and hemodynamic response of PAP to vasodilators is essential for evaluating the reversibility of PH and making treatment decisions. J Pediatr Surg 34:1779-1781. Copyright o 7999 by W.B. Saunders Company.

P

Case 2

ULMONARY HYPERTENSION (PH) occasionally is associated with chronic liver disease.1-6 The etiology of PH with liver disease is still undetermined. The treatment of PH, including liver transplantation or liver-lung transplantation remains controversial.1,3.5-13Although patients with biliary atresia may go on to have chronic liver disease, few reports have described occurrence of PH in biliary atresia patients.“J4J5 We report on 2 patients with biliary atresia, in whom PH developed during long-term follow-up after hepatoportoenterostomy. CASE

REPORTS

Hepatoportoenterostomy was performed in a girl at 48 days of age, and she had been free from jaundice ever since. Portal hypertension gradually developed as manifested by esophageal varices and hypersplenism. She underwent distal splenorenal shunt at the age of 8 years. At the age of 14 years. she started to complain of dyspnea on exertion. A chest x-ray showed enlarged right heart and increased pulmonary vascular shadow. An echocardiography casted suspicion of mild PH. At that time, her symptoms improved with alpha*-blocker and calcium antagonist. Cardiac catheterization and hemodynamic investigation at the age of 19 years showed high pulmonary arterial pressure (PAP) of 99/37 (58) mm Hg and remarkably increased pulmonary vascular resistance index (PVRI) of 1,011 (normal control, 80 to 130) dyne X set X m2/cm5 (Table 1). PAP did not decrease in response to administration of nitric oxide, prostaglandin I? or phosphodiesterase inhibitor. At the age of 20 years, she suffered from respiratory tract infection, and soon after severe right heart failure developed. Her heart failure was not improved by intensive management, and she subsequently died. Postmortum findings exhibited remarkably enlarged pulmonary trunk (Fig 1) and unique histological features of pulmonary artery wall with severe thickening of the tunica media and proliferation of the endothelial layer causing severe luminal stenosis (grade III of Heath-Edwards classification; Fig 2).16 No 12 (December),

WORDS: hypertension,

Pulmonary hypertension, distal splenorenal shunt,

biliary atresia, livertransplan-

A 17-year-old boy underwent hepatoportoenterostomy at the age of 45 days, followed by disappearance of jaundice. However, esophageal varices and hypersplenism gradually developed, and he underwent distal splenorenal shunt at the age of 3 years. At the age of 5 years, he was noticed to have cyanosis caused by pulmonary arteriovenous shunt, which disappeared spontaneously by the age of 10 years. He started to complain of dyspnea on exertion and palpitation at the age of 15 years. Cardiac catheterization and hemodynamic investigation showed high PAP of 67/32 (48) mm Hg and remarkably increased PVRI of 792 dyne X set X m%mi, which did not respond to vasodilators (Table 1). He is listed as a candidate for possible liver or liver-lung transplantation. DISCUSSION

Case 1

Journa/offediatricSurgery,Vol34,

INDEX portal tation.

1999: pp 1779-1781

Pulmonary hypertension (PH) is recognized as a component of hepatopulmonary syndrome as well as pulmonary arteriovenous shunt and is associated with many kinds of chronic liver disease.‘-6 Incidence of this combination has been reported to be 0.7% to 2% of chronic liver disease when portal hypertension or portosystemic shunt is present.‘m6 Although the etiology of pulmonary hypertension remains undetermined, a hypothesis has been proposed to explain the association of pulmonary hypertension and chronic liver disease.1-6J7A

From the Departments of Pediatric Surgery and Pediatrics, Osaka University Medical School, Osaka, Japan. Presented at the 32nd Anmcal Meeting of the Pacific Association of Pediatric Surgeons, Beijing, China, May 9-13. 1999 Address reprint reqwsts to Akira Okadn, MD, PhD, Professor and Chairman, Department of Pediatric Surgery Osaka University Medical School, 2-2 Yamndaoka, Suita City, Osaka, Japan 5650871. Copyright 0 1999 by WB. Saunders Company 0022-3468/99/3412-0006$03.00/O 1779

SOH

1780

Table

1. Hemodynamic

Investigation PDE Inhibitor

NO Rest

ET AL

(20PPrn)

PGIZ

94/38 (55)

100/42 (60)

1,196

1,283

Case 1 116173 (93)

AoP (mm Hg) PAP (mm Hg) PVRI (dyne

99/37

set X mZ/cmS) Cl (Umin/mz) Case 2 AoP (mm

Hg)

PAP (mm

Hg)

PVRI (dyne x set X m*/cm5) Cl (Umin/mz) Abbreviations:

(58)

88/28

(53)

x 1,011

1,110

3.9 115166 (84) 74/35

(51)

813

75/34

(50)

73/50 (34)

829

813

3.9 PAP, pulmonary

arterial

pressure;

AoP, aortic

sure; PVRI, pulmonary vascular resistance index; Cl, cardiac NO, nitric oxide; PGl>, prostagrandine I?; PDE, phosphodiesterase.

presindex;

possible factor is spontaneous or surgical portosystemic shunt.1-6J7It is believed that pulmonary vasoconstriction is one possible causative factor in plexogenic type of pulmonary hypertension resulting from the passage of gut-derived vasoactive substances directly into the systemic circulation via portosystemic shunts that bypass normal hepatic metabolism.‘-‘jJ7 Possible vasoconstrictive agents include histamine, serotonin, purine, pyrimidine, neuropeptide Y, and thromboxanes.lM6.17 PH associated with chronic liver disease progresses insidiously and without symptoms until the advanced stage.1-6,11,14,15.17 Wh en the patient with chronic liver disease presents with symptoms such as shortness of breath, dyspnea, or palpitation, PH often is very severe. When PH is advanced, the patient may have risk of sudden death from right heart failure14J5J7 as in our case 1. Diagnosis of PH should be made before the symptoms are noticeable. Therefore, close monitoring of PAP using routine echocardiography or cardiac catheterization may be important in the long-term follow-up of biliary atresia patients, particularly those with portal hypertension. Initial treatment of PH in chronic liver disease is

Fig 1. Postmortum findings of the heart exhibited remarkably enlarged pulmonary trunk. Ao, aorta; PA, pulmonary artery.

Fig 2. Histological findings of the pulmonary artery wall showed severe thickening of the tunica media and endothelial proliferation. The lumen was severely stenotic. By Heath-Edwards classification,16 it showed grade Ill. (H&E, original magnification x40.)

administration of oxygen and vasodilators such as alphaiblocker or calcium antagonist.1-6J7 In case 1, her symptoms were initially relieved in response to the medications, and the affected pulmonary vessels seemed reversible at that time. Also, in some recent reports, PH has been decreased in response to long-term use of vasodilators until the time of liver transplantation.12J3 However, in the advanced stage, pathological findings of the pulmonary vessels may become irreversible, and vasodilator will probably not be an effective long-term solution. In contrast to the initial improvement, case 1 did not respond to intensive therapy before death, and histopathologic findings of the pulmonary artery showed severe thickening of the tunica media and proliferation of the endothelial layer causing severe luminal stenosis. Liver transplantation has been suggested in patients with PH combined with chronic liver disease, although reversibility of PH by liver transplantation is still controversia1.3,6-13According to several reports, patients with PH survived after liver transplantation when PH was mild to moderate or controllable by using vasodilators including nitric oxide during and after liver transplantation.7,8J0J1 However, patients with severe PH eventually died of right heart failure, because PAP did not decrease despite intensive use of vasodilators.g In such patients, isolated liver transplantation may be a contraindication. As our experience with multiorgan transplantation increases, liver and lung transplantation should be considered. The hemodynamic response of PAP to vasodilators may be helpful in evaluating the reversibility of PH and making decisions for long-term treatment. PH may grow insidiously even after successful hepatoportoenterostomy and subsequent splenorenal shunt in biliary atresia patients. Careful monitoring of PAP and hemodynamic response of PAP to vasodilators is essential for evaluating the reversibility of PH and making long-term treatment decisions.

PULMONARY

HYPERTENSION

IN BILIARY

1781

ATRESIA

REFERENCES 1. Lockhart A: Pulmonary arterial hypertension in portal hypertension. Clin Gastroenterol 14:123-139, 1985 2. Edwards BS, Weir EK, Edwards WD, et al: Coexisting pulmonary and portal hypertension: Morphologic and clinical features. J Am Co11 Cardiol 10:1233-1238, 1987 3. Krowka MJ, Cortese DA: Hepatopulmonary syndrome: An evolving perspective in the era of liver transplantation. Hepatology 11:138142,1990 4. Hadengue A, Benhayoun MK, Lebrec D, et al: Pulmonary hypertension complicating portal hypertension: Prevalence and relation to splanchnic hemodynamics. Gastroenterology 100:520-528, 1991 5. Robalino BD, Moodie DS: Association between primary pulmonary hypertension and portal hypertension: Analysis of its pathophysiology and clinical, laboratory and hemodynamic manifestations. J Am Co11 Cardiol17:492-498, 1991 6. Krowka MJ, Cortese DA: Pulmonary aspects of liver disease and liver transplantation. Clin Chest Med 10:593-617, 1989 7. Scott V, Wolf AD, Kang Y, et al: Reversibility of pulmonary hypertension after liver transplantation: A case report. Transplant Proc 25:1789-1790, 1993 8. Yoshida EM, Erb SR, Pflugfelder PW, et al: Single-lung versus liver transplantation for the treatment of portopulmonary hypertension: A comparison of two patients. Transplantation 55:688-690, 1993 9. Ramsey MAE, Simpson BR, Nguyen AT. et al: Severe pulmonary hypertension in liver transplant candidates. Liver Transplant Surg 3:494-500,

1997

10. Wolf AMD, Scott V, Bjerke R, et al: Hemodynamic effects of inhaled nitric oxide in four patients with severe liver disease and pulmonary hypertension. Liver Transpl Surg 3:594-597, 1997 11. Losay J, Piot D, Bougaran J, et al: Early liver transplantation is crucial in children with liver disease and pulmonary artery hypertension. J Hepatol28:337-342, 1998 12. Plotokin JS, Cuo PC, Rubin LJ, et al: Successful use of chronic epoprostenol as a bridge to liver transplantation on severe portopulmonary hypertension. Transplantation 65:457-459, 1998 13. Kawarasaki H, Itoh M, Yoshini H, et al: Association of pulmonary hypertension and hepato-pulmonary syndrome with biliary atresia. Jpn J Pediatr Surg 31:273-276,1999 14. Moscoso G, Mieli-Vergani G, Mowat P, et al: Sudden death caused by unsuspected pulmonary arterial hypertension: 10 years after surgery for extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 12:38X-393, 1991 15. Schuijtvlot ET. Bax NMA. Houwen RHJ, et al: Unexpected lethal pulmonary hypertension in a 5-year-old girl successfully treated for biliary atresia. J Pediatr Surg 30:589-590, 1995 16. Heath D, Edwards JE: The pathology of hypertensive pulmonary vascular disease: A description of six stages of structural changes in the pulmonary arteries with special reference to congenital cardiac septal defects. Circulation l&533-547, 1958 17. Bemthal AC, Eybal CE, Payne JA: Primary pulmonary hypertension after portocaval shunt. J Clin Gastroenterol5:353-356, 1983