Long-term postsurgical outcome of biliary atresia

Long-Term By Tadaharu

Okazaki,

Postsurgical

Hiroyuki

Kobayashi,

Outcome

Atsuyuki Tokyo,

Background/Purpose: A successful Kasai procedure is effective in creating biliary drainage and radically altering the natural history of infants with biliary atresia (BA). Since its introduction in the 195Os, long-term follow-up would appear to show that only 30% to 50% of patients have a good long-term prognosis despite initially good surgical outcome. The authors reviewed their experience in treating BA from 1968 to 1997 to assess long-term outcome.

Yamataka,

of Biliary Geoffrey

Atresia

J. Lane,

and

Takeshi

Miyano

Japan

years) in group B. Recently, four group A patients (mean age, 19.3 I 1.9 years) shifted to group B because of sudden deterioration in condition involving severe CG with multiple bile lakes (n = Z), uncontrollable intestinal bleeding (n = I), and liver atrophy (n = 1). Survival deteriorated with length of follow-up. There were three survivors from 34 patients treated in period I, 16 survivors from 81 patients treated in period II (three had LT), and 29 survivors from 48 patients treated in period Ill (I 1 had LT).

Materials and Methods: The records of 163 patients treated surgically for BA from 1968 to 1997 were reviewed. Fortyeight (29%) were alive at the end of 1997, of whom, 14 had received liver transplants (LT). Surviving patients who had not undergone transplantation were divided into two groups according to clinical condition: group A, normal liver function without cholangitis (CG) and portal hypertension (PH) and group B, liver dysfunction with CG or PH. The study period was divided arbitrarily into three periods, 1968 to 1975 (period I, n = 34); 1976 to 1985 (period II, n = 81); 1986 to 1997 (period Ill, n = 48).

Conclusions: Although satisfactory bile drainage can be obtained with portoenterostomy, our data suggest that liver function can deteriorate progressively, with a possible turning point in late adolescence, indicating that as the length of follow-up increases, clinical assessment should be regular and comprehensive. The timing of LT in postoperative BA patients with deteriorating liver function is a vital management issue. J Pediatr Sorg 34:312-315. Copyright o 1999 by W.B. Saunders Company.

Resu&s:Thirty-four of 1997. There years) in group

INDEX WORDS: Biliary liver transplantation.

patients were alive without LT at the end were eight patients (mean age, 16.3 ? 4.8 A, and 26 patients (mean age, 14.3 t 7.6

L

IVER TRANSPLANTATION (LT) has become a powerful option for the management of patients with biliary atresia (BA),‘-* but the Kasai portoenterostomy is still the principal treatment modality in many pediatric surgical institutions. Effective bile drainage is obtained in 25% to 90% of patients, and some achieve good long-term prognosis. 9-15 However, the question remains whether this “good” prognosis is time related. The aim of this study was to review the patients treated for BA at our hospital from 1968 to 1997 and analyze their long-term outcome after portoenterostomy. MATERIALS

AND

From the Department of Pediatric Surgery, Juntendo University School of Medicine, Tokyo, Japan. Presented at the 45th Annual International Congress of the British Association of Paediatric Surgeons, Bristol, England, July 21-24, 1998. Address reprint requests to Takeshi Miyano, MD, PhD, Professor and Head, Department of Pediatric Surgery, Juntendo University School oj Medicine, 2-l-l Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Copyright o 1999 by WB. Saunders Company

312

portoenterostomy,

prognosis,

status was evaluated by assessing liver function results, abdominal ultrasonography findings, computed tomography (CT), and esophagoscopy. They were grouped into one of three periods according to the timing of primary surgery: 1968 to 1975 (period I, n = 34); 1976 to 1985 (period II, n = 81); and 1986 to 1997 (period III, n = 48). Forty-eight of these 163 patients were alive at the end of 1997 and were undergoing follow-up. Fourteen of these patients had received liver transplants (LT). Surviving patients who had not received LT were divided into two groups according to clinical condition: group A, normal liver function without cholangitis (CG) or portal hypertension (PH) and group B, liver dysfunction with CG or PH. We compared these two groups according to age at primary surgery, surgical procedure performed, type of BA,16 degree of liver fibrosis at the time of surgery,17 and incidence of CG or PH.

METHODS

During the period from 1968 to 1997, 163 children with BA were treated surgically at our institution. All patients whose surgery was successful were reexamined regularly as outpatients. Their clinical

0022-3468/99/3402-OOI8$03.00/0

atresia,

RESULTS

Figure 1 shows postoperative outcome at the end of 1997. Survival deteriorated as length of follow-up increased. There were three survivors from 34 patients treated in period I (9% survival rate), 16 survivors from 81 patients treated in period II (20% survival rate; three of whom had LT), and 29 survivors from 48 patients treated in period III (60% survival rate; 11 of whom had LT). Twenty-nine percent of patients (48 of 163) were alive at the end of 1997. Thirty-four patients were alive without LT at the end of 1997. Twenty-two of the 34 surviving patients who did not receive LT have survived Journal

ofPediatric.Surgery,

Vol34,

No 2 (February),

1999: pp 312-315

POSTSURGICAL

OUTCOME

OF BILIARY

313

ATRESIA

i 1976-1985 (n=81)

1968-1975 (n=34)

1986-1997 (n=48)

Period

Fig 1.

Postsurgical

outcome

at the end of 1997.

for 10 years or more. They have been mainly jaundice free postoperatively, although some have had transient episodes of elevated serum bilirubin. When we divided the surviving 34 patients into two groups according to clinical condition, there were only eight patients (mean age, 16.3 + 4.8 years) in group A, whereas the remaining 26 patients (mean age, 14.3 2 7.6 years) formed group B and are considered to be at risk for requiring LT. Clinical and pathological data for groups A and B are shown in Table 1. The number of type III BA patients was larger, and the degree of liver fibrosis at the time of primary surgery was relatively advanced in group B compared with group A. Recently, four patients previously in group A (mean age, 19.3 years) suddenly shifted to group B. Two of them had severe cholangitis with multiple bile lakes, one had uncontrollable intestinal bleeding that occurred around the anastomotic area of the stroma of a Suruga II procedure, and one had severe liver dysfunction secondary to atrophy of the left lobe of the liver. Figure 2 shows computed tomography (CT) and angiography of these cases. Table 1. Clinical

and Pahological

Data for Survivors

GroupA(n Age

(yr)

Age at primary Operative Kasai Suruga

surgery

(d)

Group B (n = 26) 14.3 -t- 7.6

79.5

62.0 i

? 27.4

23.7

procedure II

Others Type of BA I II Ill Degree Fl

= 8)

16.3 i 4.8

of liver fibrosis

2

12

6

8

0

6

6

4

0

2

2

20

at surgery

F2 F3

4

7

1

8

1

1

Unknown Episodes of cholangitis

2

10

0

22

Episodes

0

17

of portal

hypertension

Fig 2. (A) CT of a 20-year-old girl from group A in whom severe cholangitis developed shows multiple bile lakes in the left lobe of the liver. (B) Superior mesenteric artery angiography of a 19-year-old girl from group A in whom uncontrollable intestinal bleeding developed shows bleeding from around the anastomotic area of a Suruga II stoma (arrows). (C) CT of a 17-year-old girl from group A shows atrophy of the left lobe of the liver (arrows).

DISCUSSION

Since Kasai described the hepatic portoenterostomy for infants with BA, the operation was adopted throughout the world as a principal treatment modality. However,

314

OKAZAKI

long-term postoperative results reported by many investigators are widely discrepant.g-15 One study from Japan concluded that postoperative outcome of BA patients is excellent, with a lo-year survival rate of more than 70% possible if corrective surgery is performed before the age of 60 days.9,10 However, a nationwide survey of the surgical section of the American Academy of Pediatrics found that the long-term survival rate was only 25%.12 Other reported survival rates include 40% to 50% from King’s College Hospital,ls 24% from Parisi and 15.9% from the Japanese Society of Pediatric Surgeons.18 In our series, the percentage of surviving patients at the end of 1997 was 29% (48 of 163) including those who had received LT, and 20% (34 of 163) not including those who had received LT. However, only 13% (22 of 163) have actually survived for more than 10 years. Essentially, our survival rates are similar to those from other centers reported above. Several factors are known to affect long-term postoperative prognosis. Many investigators have reported that there is a correlation between hepatic fibrosis and surgical outcome in patients with BA.12,14,15Some also believe that the preoperative liver biopsy can predict the outcome of portoenterostomy.2 We have reported previously that the degree of hepatic fibrosis is correlated to clearance of jaundice after surgery. I9 Although surviving patients in both groups A and B were jaundice free at the end of 1997, at the time of initial surgery, 50% of group A patients had Fl level fibrosis and 12.5% had F2 level fibrosis, whereas 27% of group B patients had Fl level fibrosis and 31% had F2 level fibrosis. This difference was statistically significant, with group B patients having more fibrosis. Moreover, the number of type III BA patients was greater in group B compared with group A. Age at the time of primary surgery is known to be correlated with surgical outcome because age influences the degree of fibrosis. 10,20It is generally believed that postoperative prognosis is good if initial surgery is performed within 60 days of birth and bad if performed after 90 to 100 days after birth.12.15 However, in our series, there was no difference between long-term survivors in groups A and B for age at the time of primary surgery (79.5 + 27.4 days for group A and 62.0 2 23.7 days for group B). However, we did confirm that initial surgery after 90 to 100 days was disadvantageous for long-term survival.

ET AL

Recently, LT has become a powerful option for the management of patients with BA. Improvements in technique and postoperative care have enabled LT to be performed with excellent survival rates of 70% to 80% even in infants less than 1 year of age.1,3-7 Some investigators have recommended that LT should be the primary surgical approach for the management of BA, whereas others have suggested that it should be reserved for the failed portoenterostomy patients. Davenport et all5 has reported that most infants in whom a portoenterostomy does not achieve bile drainage require LT within the first 2 years of life, but that some may not need LT until 5 or 10 years of age because of slower deterioration in liver function. However, it also has been reported that most jaundice-free patients have no major problems provided they have precise postoperative follow-up care,i8 with liver dysfunction showing a tendency to decrease in frequency and severity after the age of 15 yearslo In this study, we never considered any of our group A survivors as possible candidates for LT because they were leading almost normal lives and were well into their teens with no evidence of liver dysfunction or CG-PH on routine follow-up investigations. However, four patients recently shifted from group A to group B because of unexpected sudden deterioration in liver function and are now considered to be candidates for LT because of persistent hyperbilirubinemia of more than 10 mg/dL, recurrent cholangitis, and massive bleeding.7~20 Information on the definitive criteria for LT, particularly in postoperative adolescent patients with BA who are long-term survivors, is scant, and is an area that warrants further research. To this end, a group of our colleagues21,22has reported recently that serum procollagen-III peptide, type IV collagen, and plasma endothelin may reflect the degree of fibrosis and PH in patients with BA, even though they may be clinically well and jaundice free. Although satisfactory bile drainage can be obtained with seemingly good prognosis post-Kasai, our data suggest that liver function can still deteriorate progressively, with a probable turning point in midadolescence. Our findings indicate there is an unfulfilled need for simple, effective, accurate markers of prognosis in postoperative BA patients to predict sudden deterioration during regular routine follow-up assessment.

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18. Ohi R, Hanamatsu M, Mochizuki I, et al: Progress in the treatment of biliary atresia. World J Surg 9:285-293, 1985 19. Miyano M, Fujimoto T, Ohya T, et al: Current concept of the treatment of biliary atresia. World J Surg 17:332-336, 1993 20. Fukui U, Kawahara H, Tanano H, et al: Indication and timing for liver transplantation in biliary atresia with persistent jaundice after portoenterostomy. J Jpn Sot Pediatr Surg 29:783-788,1993 21. Kobayashi H, Miyano T, Horikoshi K, et al: Prognostic value of serum procollagen III peptide and type IV collagen in patients with biliaty atresia. J Pediatr Surg 33:112-114, 1998 22. Kobayashi H, Miyano T, Horikoshi K, et al: Clinical significance of plasma endothelin in patients with biliary atresia. Pediatr Surg Int 13:491-493, 1998