Hye Kyung Chang, JungHye Kyung Chang, JungHye Kyung Chang, JungHye Kyung Chang, Jung----Tak Oh, Seung Hoon Choi, Seok Joo HanTak Oh, Seung Hoon Choi, Seok Joo HanTak Oh, Seung Hoon Choi, Seok Joo HanTak Oh, Seung Hoon Choi, Seok Joo Han

Division of Pediatric Surgery, Department of Surgery,Division of Pediatric Surgery, Department of Surgery,Division of Pediatric Surgery, Department of Surgery,Division of Pediatric Surgery, Department of Surgery,Yonsei University College of MedicineYonsei University College of MedicineYonsei University College of MedicineYonsei University College of Medicine

Home Intravenous Antibiotic Treatment for Home Intravenous Antibiotic Treatment for Home Intravenous Antibiotic Treatment for Home Intravenous Antibiotic Treatment for Intractable Cholangitis in Biliary AtresiaIntractable Cholangitis in Biliary AtresiaIntractable Cholangitis in Biliary AtresiaIntractable Cholangitis in Biliary Atresia

BackgroundBackgroundBackgroundBackgroundCholangitisCholangitisCholangitisCholangitis

common complication during follow up of biliary atresia after Kasai operation

Intractable Cholangitis (IC)Intractable Cholangitis (IC)Intractable Cholangitis (IC)Intractable Cholangitis (IC)

- uncontrolled cholangitis by routine conservative treatment

-may cause biliary cirrhosis, hepatic failure, portal hypertension

- most important and difficult complicationin management after Kasai portoenterostomy

: poor prognosis and the occasional requirement of liver transplantation

Intrahepatic Biliary CystIntrahepatic Biliary CystIntrahepatic Biliary CystIntrahepatic Biliary Cyst

may be the source of biliary infection

BackgroundBackgroundBackgroundBackground

- review of the effects and the role of home intravenous antibiotic treatment (HIVA) in 8 patients of post-Kasai intractable cholangitis with

biliary atresia

- suggestion of HIVA as an effective method for management of intractable cholangitis and intrahepatic biliary cysts in post-Kasai patients

Management of intractable cholangitis and intrahepatic biliary cManagement of intractable cholangitis and intrahepatic biliary cManagement of intractable cholangitis and intrahepatic biliary cManagement of intractable cholangitis and intrahepatic biliary cystsystsystsysts

- many surgical or medical trialsto control cholangitis and intrahepatic biliary cysts

- no treatment of choice of intractable cholangitis or intrahepatic biliary cysts

PurposePurposePurposePurpose

retrospective review of medical recordsretrospective review of medical recordsretrospective review of medical recordsretrospective review of medical recordsfor whom

- treated by HIVA for IC after successful Kasai portoenterostomy with BA - from 1998 to 2008- at Severance Hospital and Yongdong Severance Hospital

diagnostic criteria of cholangitisdiagnostic criteria of cholangitisdiagnostic criteria of cholangitisdiagnostic criteria of cholangitis

1)clinical symptoms such as fever, abdominal pain, jaundice or acholic stool2)laboratory data such as hyperbilirubinemia, elevated liver enzyme

or isolation of bacteria on blood culture3)without other fever focus such as upper respiratory tract infection or

urinary tract infection

MethodsMethodsMethodsMethods

diagnostic criteria of intractable cholangitisdiagnostic criteria of intractable cholangitisdiagnostic criteria of intractable cholangitisdiagnostic criteria of intractable cholangitis

recurrent cholangitis unresponsive to conservative managementwith intravenous antibiotics treatment

1)duration of admission for treatment longer than 1 month

2)three times of admission due to cholangitiswith duration between previous discharge and readmission

less than 1 month

detection of intrahepatic biliary cystdetection of intrahepatic biliary cystdetection of intrahepatic biliary cystdetection of intrahepatic biliary cyst

Abdominal ultrasonographyAbdominal CT

central venous catheter indwellingcentral venous catheter indwellingcentral venous catheter indwellingcentral venous catheter indwelling

during the HIVA treatment

MethodsMethodsMethodsMethods

ResultsResultsResultsResultsIntractable cholangitis (IC) after successful Kasai operation

in 10 cases during last decade

to settle IC, intrahepatic cysts were drained in the first two patientsbut IC was not controlled

Intrahepatic cysts in case IIntrahepatic cysts in case IIntrahepatic cysts in case IIntrahepatic cysts in case I Remained intrahepatic cysts after Remained intrahepatic cysts after Remained intrahepatic cysts after Remained intrahepatic cysts after hepatic cystojejunostomy in case Ihepatic cystojejunostomy in case Ihepatic cystojejunostomy in case Ihepatic cystojejunostomy in case I

ResultsResultsResultsResultsHIVA program in the patients diagnosed as ICHIVA program in the patients diagnosed as ICHIVA program in the patients diagnosed as ICHIVA program in the patients diagnosed as IC

after insertion of central venous catheterwith help of home care nursing in 10 cases

two patients of initial period of HIVA were not followed upbecause of transfer to other hospital

Duration of HIVADuration of HIVADuration of HIVADuration of HIVA

from 8 to 39 months with median value of 13.5 months

two patients on HIVAduration of 8 months for one patient and 15 months for the other

six patients off HIVAfrom 8 to 39 months of duration with median value of 14 months

Patient Patient Patient Patient NumberNumberNumberNumber

SexSexSexSexAge of Kasai Age of Kasai Age of Kasai Age of Kasai op. (months)op. (months)op. (months)op. (months)

Age of ICAge of ICAge of ICAge of IC(months)(months)(months)(months)

IHCIHCIHCIHCAge of HIVA Age of HIVA Age of HIVA Age of HIVA

(months)(months)(months)(months)Duration b/w IC Duration b/w IC Duration b/w IC Duration b/w IC ––––

HIVA (months)HIVA (months)HIVA (months)HIVA (months)

1111 FFFF 2222⅓⅓⅓⅓ 6666 YYYY 60606060 44444444

2222 MMMM 2222⅔⅔⅔⅔ 5555 YYYY 33333333 28282828

3333 FFFF 2222 8888 YYYY 10101010 2222

44441)1)1)1) FFFF 11111111////2222 5555 YYYY 9999 4444

5555 FFFF 1111⅓⅓⅓⅓ 12121212 YYYY 12121212 0000

6666 FFFF 11111111////2222 4444 YYYY 5555 1111

7777 FFFF 11112222////3333 12121212 NNNN 13131313 1111

8888 FFFF 22221111////2222 35353535 YYYY 36363636 1111

Clinical Characteristics of Patients on HIVAClinical Characteristics of Patients on HIVAClinical Characteristics of Patients on HIVAClinical Characteristics of Patients on HIVA

IC : intractable cholangitisIC : intractable cholangitisIC : intractable cholangitisIC : intractable cholangitisIHC : intrahepatic cystIHC : intrahepatic cystIHC : intrahepatic cystIHC : intrahepatic cystHIVA : home intravenous antibiotic treatmentHIVA : home intravenous antibiotic treatmentHIVA : home intravenous antibiotic treatmentHIVA : home intravenous antibiotic treatment1) Kasai op. at other hospital1) Kasai op. at other hospital1) Kasai op. at other hospital1) Kasai op. at other hospital

PTBDPTBDPTBDPTBDAlcohol sclerosing Tx.Alcohol sclerosing Tx.Alcohol sclerosing Tx.Alcohol sclerosing Tx.

Alcohol Alcohol Alcohol Alcohol sclerosing Tx.sclerosing Tx.sclerosing Tx.sclerosing Tx.

PTBDPTBDPTBDPTBD

Hepatic cystojejunostomyHepatic cystojejunostomyHepatic cystojejunostomyHepatic cystojejunostomy

Revision of Revision of Revision of Revision of portoenterostomyportoenterostomyportoenterostomyportoenterostomy

PTBDPTBDPTBDPTBDMetal stent insertionMetal stent insertionMetal stent insertionMetal stent insertion

Clinical CoursesClinical CoursesClinical CoursesClinical Courses

Clinical CoursesClinical CoursesClinical CoursesClinical Courses

ShortShortShortShort----term Results of HIVAterm Results of HIVAterm Results of HIVAterm Results of HIVA

Patient Patient Patient Patient NumberNumberNumberNumber

Duration of HIVADuration of HIVADuration of HIVADuration of HIVA(months)(months)(months)(months)

Disappearance of IHCDisappearance of IHCDisappearance of IHCDisappearance of IHC1)1)1)1) Duration of Initial Ch.Duration of Initial Ch.Duration of Initial Ch.Duration of Initial Ch.----free Status free Status free Status free Status after HIVA (months)after HIVA (months)after HIVA (months)after HIVA (months)

1111 18181818 YYYY 42424242

2222 16161616 YYYY 13131313

3333 8888 YYYY 13131313

4444 39393939 YYYY 13131313

5555 9999 YYYY 52525252

6666 12121212 YYYY 31313131

7777 15 (on Tx.)15 (on Tx.)15 (on Tx.)15 (on Tx.) ----2)2)2)2) 3333

8888 8 (on Tx.)8 (on Tx.)8 (on Tx.)8 (on Tx.) NNNN 3333

IHC : intrahepatic cystIHC : intrahepatic cystIHC : intrahepatic cystIHC : intrahepatic cystCh. : cholangitisCh. : cholangitisCh. : cholangitisCh. : cholangitis1)1)1)1) detected by imaging studies (abd. U/S or CT)detected by imaging studies (abd. U/S or CT)detected by imaging studies (abd. U/S or CT)detected by imaging studies (abd. U/S or CT)2)2)2)2) no previously detected intrahepatic cystno previously detected intrahepatic cystno previously detected intrahepatic cystno previously detected intrahepatic cyst

PatientPatientPatientPatientNumberNumberNumberNumber

Duration of Duration of Duration of Duration of AdmissionAdmissionAdmissionAdmission1)1)1)1)

before HIVAbefore HIVAbefore HIVAbefore HIVA(days)(days)(days)(days)

DurationDurationDurationDurationbefore HIVAbefore HIVAbefore HIVAbefore HIVA(months)(months)(months)(months)2)2)2)2)

AdmissionAdmissionAdmissionAdmissionRatioRatioRatioRatio3)3)3)3) beforebeforebeforebefore

HIVAHIVAHIVAHIVA

Duration ofDuration ofDuration ofDuration ofAdmissionAdmissionAdmissionAdmission1)1)1)1)

after HIVAafter HIVAafter HIVAafter HIVA(days)(days)(days)(days)

DurationDurationDurationDurationafter HIVAafter HIVAafter HIVAafter HIVA(months)(months)(months)(months)4)4)4)4)

AdmissionAdmissionAdmissionAdmissionRatioRatioRatioRatio3)3)3)3) afterafterafterafter

HIVAHIVAHIVAHIVA

1111 318318318318 73737373 4.44.44.44.4 7777 36363636 0.20.20.20.2

2222 287287287287 29292929 9.99.99.99.9 58585858 55555555 1.11.11.11.1

3333 109109109109 12121212 9.19.19.19.1 102102102102 51515151 2.02.02.02.0

4444 232232232232 45454545 5.25.25.25.2 0000 9999 0.00.00.00.0

5555 93939393 15151515 6.26.26.26.2 0000 43434343 0.00.00.00.0

6666 67676767 13131313 5.25.25.25.2 0000 26262626 0.00.00.00.0

7777 70707070 10101010 7.07.07.07.0 616161615)5)5)5) 13131313 4.74.74.74.7

8888 141141141141 30303030 4.74.74.74.7 262626265)5)5)5) 8888 3.33.33.33.3

MedianMedianMedianMedian 125125125125 22222222 5.75.75.75.7 16.516.516.516.5 31313131 0.60.60.60.6

1) Admission due to cholangitis1) Admission due to cholangitis1) Admission due to cholangitis1) Admission due to cholangitis2) Duration from diagnosis of intractable cholangitis to HIVA2) Duration from diagnosis of intractable cholangitis to HIVA2) Duration from diagnosis of intractable cholangitis to HIVA2) Duration from diagnosis of intractable cholangitis to HIVA3) Admission days / duration in months3) Admission days / duration in months3) Admission days / duration in months3) Admission days / duration in months4) Duration from HIVA to last follow up4) Duration from HIVA to last follow up4) Duration from HIVA to last follow up4) Duration from HIVA to last follow up5) Admission during HIVA5) Admission during HIVA5) Admission during HIVA5) Admission during HIVA

Effect of HIVA on Admission Rate due to CholangitisEffect of HIVA on Admission Rate due to CholangitisEffect of HIVA on Admission Rate due to CholangitisEffect of HIVA on Admission Rate due to Cholangitis

1) Wilcoxon Signed Ranks Test1) Wilcoxon Signed Ranks Test1) Wilcoxon Signed Ranks Test1) Wilcoxon Signed Ranks Test

Before HIVA Before HIVA Before HIVA Before HIVA After HIVAAfter HIVAAfter HIVAAfter HIVA PPPP----ValueValueValueValue1)1)1)1)

5.7 (4.4 5.7 (4.4 5.7 (4.4 5.7 (4.4 ---- 9.9)9.9)9.9)9.9) 0.6 (0.0 0.6 (0.0 0.6 (0.0 0.6 (0.0 –––– 4.7)4.7)4.7)4.7) 0.0120.0120.0120.012

Admission RatioAdmission RatioAdmission RatioAdmission Ratio(Admission days / duration in months) (Admission days / duration in months) (Admission days / duration in months) (Admission days / duration in months)

Effect of HIVA on Admission Rate due to CholangitisEffect of HIVA on Admission Rate due to CholangitisEffect of HIVA on Admission Rate due to CholangitisEffect of HIVA on Admission Rate due to Cholangitis

Results of HIVAResults of HIVAResults of HIVAResults of HIVA

LongLongLongLong----term Results of HIVAterm Results of HIVAterm Results of HIVAterm Results of HIVA

Patient Patient Patient Patient NumberNumberNumberNumber

Duration of Duration of Duration of Duration of FollowFollowFollowFollow----up after up after up after up after HIVA (months)HIVA (months)HIVA (months)HIVA (months)

Ch. on Last Ch. on Last Ch. on Last Ch. on Last FollowFollowFollowFollow----upupupup

Duration of Last Duration of Last Duration of Last Duration of Last Ch.Ch.Ch.Ch.----free Status free Status free Status free Status

after HIVA after HIVA after HIVA after HIVA (months)(months)(months)(months)

Recurrence of Recurrence of Recurrence of Recurrence of IHCIHCIHCIHC1)1)1)1)

Duration of IHCDuration of IHCDuration of IHCDuration of IHC----free Status free Status free Status free Status (months) (months) (months) (months)

1111 37373737 YYYY 42424242 YYYY 35353535

2222 47474747 YYYY 27272727 YYYY 34343434

3333 51515151 NNNN 12121212 NNNN 33333333

4444 9999 NNNN 13131313 NNNN 50505050

5555 43434343 NNNN 52525252 NNNN 42424242

6666 24242424 NNNN 31313131 NNNN 32323232

7777 ----2)2)2)2) NNNN 3333 ----3)3)3)3) ----3)3)3)3)

8888 ----2)2)2)2) NNNN 3333 ----2)2)2)2) ----2)2)2)2)

Ch. : cholangitis, IHC : intrahepatic cystCh. : cholangitis, IHC : intrahepatic cystCh. : cholangitis, IHC : intrahepatic cystCh. : cholangitis, IHC : intrahepatic cyst1)1)1)1) detected by imaging studies (abd. U/S or CT)detected by imaging studies (abd. U/S or CT)detected by imaging studies (abd. U/S or CT)detected by imaging studies (abd. U/S or CT)2)2)2)2) on HIVA treatmenton HIVA treatmenton HIVA treatmenton HIVA treatment3)3)3)3) no previously detected intrahepatic cystno previously detected intrahepatic cystno previously detected intrahepatic cystno previously detected intrahepatic cyst

LongLongLongLong----term Results of HIVAterm Results of HIVAterm Results of HIVAterm Results of HIVA

Patient Patient Patient Patient NumberNumberNumberNumber

Age on Last Age on Last Age on Last Age on Last FollowFollowFollowFollow----up (yrs)up (yrs)up (yrs)up (yrs)

T.Bb (mg/dL)T.Bb (mg/dL)T.Bb (mg/dL)T.Bb (mg/dL) Alb (g/dL)Alb (g/dL)Alb (g/dL)Alb (g/dL) PT (INR)PT (INR)PT (INR)PT (INR) Ascites*Ascites*Ascites*Ascites*

1111 10101010 1.11.11.11.1 3.93.93.93.9 1.281.281.281.28 NNNN

2222 8888 0.70.70.70.7 3.93.93.93.9 1.551.551.551.55 NNNN

3333 5555 0.60.60.60.6 5.05.05.05.0 1.021.021.021.02 NNNN

4444 4444 0.90.90.90.9 4.94.94.94.9 0.990.990.990.99 NNNN

5555 5555 2.12.12.12.1 3.13.13.13.1 1.061.061.061.06 NNNN

6666 3333 0.70.70.70.7 5.25.25.25.2 1.151.151.151.15 NNNN

7777 2222 0.90.90.90.9 3.93.93.93.9 1.131.131.131.13 NNNN

8888 3333 1.21.21.21.2 3.53.53.53.5 1.161.161.161.16 SmSmSmSm

T.Bb : serum total bilirubin, Alb : serum albuminT.Bb : serum total bilirubin, Alb : serum albuminT.Bb : serum total bilirubin, Alb : serum albuminT.Bb : serum total bilirubin, Alb : serum albuminPT : prothrombin time, INR : international normalized ratio of PPT : prothrombin time, INR : international normalized ratio of PPT : prothrombin time, INR : international normalized ratio of PPT : prothrombin time, INR : international normalized ratio of PTTTTSm : small amount of ascites, * : detected in U/S or CTSm : small amount of ascites, * : detected in U/S or CTSm : small amount of ascites, * : detected in U/S or CTSm : small amount of ascites, * : detected in U/S or CT

-Intractable cholangitis after successful Kasai portoenterostomy can be controlled by HIVA treatment with statistically significantreduction of admission period due to cholangitis (p=0.012).

-The duration of cholangitis free in HIVA-off group ranged from 12 to 52 months (median value of 29 months).

-Intrahepatic cysts related to intractable cholangitis also can becontrolled and disappeared by HIVA treatment.

- Hepatic function is maintained good in all 8 patients of HIVA.

SummarySummarySummarySummary

ConclusionConclusionConclusionConclusion

-HIVA may be an effective primary treatment for intractablecholangitis after Kasai operation in biliary atresia.

-All of the 8 patients with HIVA for IC have tolerable hepatic function by control of cholangitis and following biliary cirrhosis. No patient required liver transplantation due to chronic liver disease or hepatic failure.

-Early application of HIVA to intractable cholangitis may help tomaintain the hepatic function without recurrence of cholangitis or intrahepatic biliary cysts.

-Early detection of intrahepatic biliary cysts or early diagnosis of intractable cholangitis are necessary for early HIVA application.