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Öztürk H, Sarı S, Sözen H, Eğritaş Gürkan Ö, Dalgıç B, Dalgıç A. Long-Term Outcomes of Patients With Progressive Familial Intrahepatic Cholestasis After Biliary Diversion. EXP CLIN TRANSPLANT 2022; 20:76-80. [PMID: 35570606 DOI: 10.6002/ect.pediatricsymp2022.o26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Progressive familial intrahepatic cholestasis is a heterogeneous group of genetic disorders characterized by disrupted bile homeostasis. Patients with this disease typically present with cholestasis and pruritus early in life and often progress to end-stage liver disease. The clinical symptoms that patients with progressive familial intrahepatic cholestasis encounter are usually refractory to medical treatment. Although the effects of biliary diversion surgery on native liver survival are not exactly known, this procedure may provide a positive impact on pruritus and laboratory parameters in these patients. MATERIALS AND METHODS We retrospectively evaluated the clinical and laboratory characteristics of patients with progressive familial intrahepatic cholestasis who underwent partial external biliary diversion between 2002 and 2020 at our center. Diagnosis of progressive familial intrahepatic cholestasis was made by clinical, biochemical, and histopathological characteristics as well as genetic testing. RESULTS Nine patients were included in the study. Five patients required liver transplant during follow-up, with 4 having liver transplant as a result of endstage liver disease (median interval of 5 years). In 1 patient, partial external biliary diversion was performed 1.5 years after liver transplant for severe diarrhea, metabolic acidosis, and hepatic steatosis. Four patients did not require liver transplant during follow-up (median follow-up time of 7.6 years). Pruritus responded well to partial external biliary diversion in all patients. Among laboratory values evaluated 6 months after biliary diversion, only albumin showed significant improvement. CONCLUSIONS Partial external biliary diversion had favorable results on long-term follow-up. This procedure can provide the relief of pruritus and delay the requirement for liver transplant in patients with progressive familial intrahepatic cholestasis. In our view, partial external biliary diversion should be considered the first-line surgical management for patients with this disease.
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Affiliation(s)
- Hakan Öztürk
- From the Department of Pediatric Gastroenterology, Gazi University, Ankara, Turkey
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Li Q, Chong C, Sun R, Yin T, Huang T, Diao M, Li L. Long-term outcome following cholecystocolostomy in 41 patients with progressive familial intrahepatic cholestasis. Pediatr Surg Int 2021; 37:723-730. [PMID: 33651176 DOI: 10.1007/s00383-021-04871-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/13/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE Progressive familial intrahepatic cholestasis (PFIC) is a cohort of autosomal recessive syndromes which presents with jaundice, severe pruritus and liver derangement. Without treatments, patients progress to liver failure in early childhood. Biliary diversion strategies have been deployed to interrupt enterohepatic circulation to alleviate symptoms and delay progression to cirrhosis. Cholecystocolostomy has been the diversion method of choice at our institution and we aim to evaluate its long-term outcome. METHODS All patients with PFIC who underwent cholecystocolostomy between August 2003 to May 2019 were included. PFIC diagnosed by clinical course, serum liver biochemistry and genotyping excluding other causes of cholestasis. All patients received ursodeoxycholic acid prior to biliary diversion. Those without long-term follow-up were excluded. Long-term follow-up conducted with physical examination, abdominal ultrasonography, liver function tests, contrast enema studies and colonoscopies. Outcome analysis was performed with patients divided into three groups according to their postoperative responses. RESULTS 58 children underwent cholecystocolostomy, 41 were included in the study. Overall survival rate was 73.2% without a liver transplant. Survival improved to 81.1% in those without cirrhosis. 83.3% of those without a transplant was to no longer need any medication after their cholecystocolostomy. Recurrent cholestasis was seen in those with constipation (n = 8), ascending cholangitis (n = 10), intrahepatic reflux from Y-loop (n = 3) and cystic duct stenosis (n = 4). CONCLUSION Cholecystocolostomy is a safe and effective technique for treatment of cholestasis in PFIC patients without cirrhosis. Careful monitoring and proactive management of postoperative constipation and ascending cholangitis is required to prevent stenosis of the cystic duct leading to recurrent cholestasis.
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Affiliation(s)
- Qianqing Li
- Department of Pediatric Surgery, Capital Institute of Pediatrics-Peking University Teaching Hospital, No. 2 Yabao Road, Beijing, 100020, China
| | - Clara Chong
- Department of Pediatric Surgery, Southampton General Hospital, Coxford Road, Southampton, SO16 5YA, UK
| | - Rui Sun
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Tong Yin
- Department of Pediatric Surgery, Capital Institute of Pediatrics-Peking University Teaching Hospital, No. 2 Yabao Road, Beijing, 100020, China
| | - Ting Huang
- Department of Pediatric Surgery, Children's Hospital Capital Institute of Pediatrics, Graduate School of Peking Union Medical College, Beijing, 100020, China
| | - Mei Diao
- Department of Pediatric Surgery, Capital Institute of Pediatrics-Peking University Teaching Hospital, No. 2 Yabao Road, Beijing, 100020, China.
| | - Long Li
- Department of Pediatric Surgery, Capital Institute of Pediatrics-Peking University Teaching Hospital, No. 2 Yabao Road, Beijing, 100020, China.
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Abstract
Progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (AS) are conditions caused by either an autosomal recessive or an autosomal dominant genetic defect, and they are both characterized by cholestasis, jaundice, and severe debilitating pruritus refractory to medical management. Before the advent of liver transplantation, most PFIC patients would die from end-stage liver disease in the first decade of life. Although liver transplantation has led to patients' survival, disease recurrence (PFIC-2) and severe extra-hepatic manifestations of the disease (PFIC-1) occurred post transplant. In the late 1980s, Whitington described the use of partial external biliary diversion in PFIC and AS patients as a successful way to improve symptoms and decrease circulating bile acid serum concentrations. Since then, other diversion techniques have been described (ileal exclusion and partial internal biliary diversion). These techniques have the benefit of avoiding a stoma, but equivalent results have not been demonstrated (recurrence of cholestasis after ileal exclusion, limited follow up after internal biliary diversion). Overall, studies have showed that biliary diversions in children with cholestasis are safe procedures with low morbidity and mortality, and that they can reduce inflammation and ongoing liver injury, therefore delaying or avoiding the need for liver transplantation in some patients.
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Foroutan HR, Bahador A, Ghanim SM, Dehghani SM, Anbardar MH, Fattahi MR, Forooghi M, Azh O, Tadayon A, Sherafat A, Yaghoobi AA, Ashraf MA. Effects of partial internal biliary diversion on long-term outcomes in patients with progressive familial intrahepatic cholestasis: experience in 44 patients. Pediatr Surg Int 2020; 36:603-610. [PMID: 32206891 DOI: 10.1007/s00383-020-04641-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/05/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE Progressive familial intrahepatic cholestasis (PFIC) is a hereditary disease characterized by cholestasis, which may cause jaundice, severe pruritus, and cirrhosis in the later stages. By the invention of biliary diversion methods, these patients were prevented from undergoing liver transplant. Using biliary diversion techniques, the entero-hepatic cycle was interrupted. This lowers the bile acid pool and resolves the pruritus. Herein, we report 44 cases of PFIC who underwent partial internal biliary diversion (PIBD) and long-term follow-up of these children. This comprises the largest case series of PIBD. METHODS All patients were diagnosed by liver biopsy as PFIC before the operation. All underwent cholecysto colic bypass by jejunal interposition due to severe pruritus unresponsive to medication. Laboratory blood tests, sonography, and physical exam were done before and after the operation once every 3 months. Besides, a questionnaire was designed to ask the patients about the symptoms after the operation, and a pruritus score was measured using the 5D-itch scale. RESULTS 44 children (25 boys, 19 girls), between 1.75 and 27.5 years (at the time of this study) were followed for a median period of 54 months. Age at operation ranged from 2 months to 18 years, with a median of 29 months. Of these children, 14 were lost to follow up. Results showed a significant decrease in pruritus and sleep disturbance after the surgery (p < 0.001). Also, jaundice decreased from 82.1 before to 7.1% following the surgery. 50% of the patients became medication-free at follow-up. CONCLUSION PIBD is a safe procedure which helps non-cirrhotic children preserve their liver function. Therefore, PIBD prevents them from undergoing liver transplant. Effective results were achieved in terms of severe pruritus and jaundice, and children were able to regain their sleep patterns. It also avoided external stoma, which is more convenient from the patient's point of view.
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Affiliation(s)
- Hamid Reza Foroutan
- Laparoscopy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran
| | - Ali Bahador
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran
| | - Sultan Mohsin Ghanim
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran
| | - Seyed Mohsen Dehghani
- Gastroenterohepatology Research Center, Department of Pediatric Gastroenterology, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Mohammad Reza Fattahi
- Department of Gastroenterology, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Forooghi
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran
| | - Omidreza Azh
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran
| | - Ali Tadayon
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran
| | - Alireza Sherafat
- School of Medicine, University of Central Lancashire, Preston, England
| | - Amir Arsalan Yaghoobi
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran
| | - Mohammad Ali Ashraf
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran.
- Student Research Committee, Shiraz University of Medical Sciences, Zand St., 71 32326645, Shiraz, Iran.
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Liu T, Wang RX, Han J, Qiu YL, Borchers CH, Ling V, Wang JS. Changes in plasma bile acid profiles after partial internal biliary diversion in PFIC2 patients. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:185. [PMID: 32309332 PMCID: PMC7154393 DOI: 10.21037/atm.2020.01.103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Background We ask if plasma bile acid profiles can be used to monitor the effectiveness of partial internal biliary diversion (PIBD) for treating uncontrolled cholestasis in progressive familial intrahepatic cholestasis type 2 (PFIC2) patients. Methods Plasma bile acids were profiled in 3 cases of ATP-binding cassette, sub-family B member 11 (ABCB11)-mutated PFIC2 children before and after PIBD compared to healthy controls and 8 PFIC2 patients. The quantitation of bile acids was performed by reversed-phase ultrahigh-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS) with negative ion detection. Results Before PIBD, all three patients presented with >50-fold higher levels of total plasma bile acids, 2-7 folds higher ratios of taurine: glycine conjugated primary bile acids, and unchanged secondary bile acids levels compared to healthy controls. After PIBD, only one of the three patients (P3) showed relief of cholestasis. The bile acid profiles of the two nonresponding patients showed little change while that of the responding patient showed a 5-fold reduction in total plasma primary bile acids, a reduced taurine: glycine conjugate ratio, and an unexpected 26- and 12-fold increase in secondary bile acids DCA and LCA respectively. One year later, the responder suffered a recurrence of cholestasis, and the bile acid profile shifted back to a more pre-PIBD-like profile. Conclusions Plasma bile acid profiles may potentially be useful as sensitive biomarkers for monitoring the clinical course of PIBD patients. Relief of cholestasis after PIBD appears to be associated with significantly increased circulating toxic secondary bile acids and this may limit the utility of PIBD in PFIC2 patients in the long run.
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Affiliation(s)
- Teng Liu
- Department of Pediatrics, Fudan University Shanghai Medical College, The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China.,BC Cancer Agency, Vancouver, British Columbia, Canada.,University of Victoria-Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada
| | - Ren-Xue Wang
- BC Cancer Agency, Vancouver, British Columbia, Canada
| | - Jun Han
- University of Victoria-Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada.,Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
| | - Yi-Ling Qiu
- Department of Pediatrics, Fudan University Shanghai Medical College, The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China
| | - Christoph H Borchers
- University of Victoria-Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada.,Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.,Gerald Bronfman Department of Oncology and Proteomics Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.,Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.,Department of Data Intensive Science and Engineering, Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Moscow, Russia
| | - Victor Ling
- BC Cancer Agency, Vancouver, British Columbia, Canada
| | - Jian-She Wang
- Department of Pediatrics, Fudan University Shanghai Medical College, The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai 201102, China
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Henkel SAF, Squires JH, Ayers M, Ganoza A, Mckiernan P, Squires JE. Expanding etiology of progressive familial intrahepatic cholestasis. World J Hepatol 2019; 11:450-463. [PMID: 31183005 PMCID: PMC6547292 DOI: 10.4254/wjh.v11.i5.450] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 04/19/2019] [Accepted: 04/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Progressive familial intrahepatic cholestasis (PFIC) refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes, resulting in a hepatocellular form of cholestasis. While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause, recent scientific advancements have uncovered multiple specific responsible proteins. The variety of identified defects has resulted in an ever-broadening phenotypic spectrum, ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.
AIM To review current data on defects in bile acid homeostasis, explore the expanding knowledge base of genetic based diseases in this field, and report disease characteristics and management.
METHODS We conducted a systemic review according to PRISMA guidelines. We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding, diagnosis, and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC. English only articles were accessed in full. The manual search included references of retrieved articles. We extracted data on disease characteristics, associations with other diseases, and treatment. Data was summarized and presented in text, figure, and table format.
RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults. A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.
CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1 (ATP8B1), BSEP (ABCB11), and MDR3 (ABCB4) transporter deficiencies, as well as more recently described gene mutations -- TJP2 (TJP2), FXR (NR1H4), MYO5B (MYO5B), and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.
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Affiliation(s)
- Sarah AF Henkel
- Division of Gastroenterology, Hepatology, and Nutrition, Emory School of Medicine, Atlanta, GA 30322, United States
| | - Judy H Squires
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, United States
| | - Mary Ayers
- Division of Gastroenterology, Hepatology, and Nutrition, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, United States
| | - Armando Ganoza
- Division of Pediatric Transplantation, Department of Surgery, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, United States
| | - Patrick Mckiernan
- Division of Gastroenterology, Hepatology, and Nutrition, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, United States
| | - James E Squires
- Division of Gastroenterology, Hepatology, and Nutrition, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, United States
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Quality of Life in Patients With Progressive Familial Intrahepatic Cholestasis: No Difference Between Post-liver Transplantation and Post-partial External Biliary Diversion. J Pediatr Gastroenterol Nutr 2018; 67:643-648. [PMID: 30052569 DOI: 10.1097/mpg.0000000000002118] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES In patients with progressive familial intrahepatic cholestasis (PFIC), partial external biliary diversion (PEBD), which is associated with a permanent stoma, is recommended as first-line therapy, whereas primary liver transplantation (LTx) is restricted to those with cirrhosis. Our aim was to quantify the health-related quality of life (HRQOL) in patients with PFIC and to evaluate whether there is a difference in their HRQOL depending on the surgical approach. METHODS A prospective HRQOL study on a consecutive series of PFIC was conducted using Pediatric Quality of Life Inventory 4.0 child-self and parent-proxy reports. Patients with PFIC after PEBD who still lived with their native livers were compared to those after LTx. Both groups were compared to healthy children. RESULTS A total of 32 patients (53% girls) patients with a mean age of 17.7 ± 7.3 years were studied. Twenty-two had undergone LTx at a mean age of 7.8 ± 3.8 years and 10 had undergone PEBD at a mean age of 4.1 ± 3.9 years. At the time of HRQOL assessment, the mean age was 18.9 ± 7.5 years in the LTx group and 15.3 ± 6.5 years in the PEBD group. Child-self and parent-proxy reports showed no significant difference in HRQOL between patients with PFIC after LTx and those after PEBD except for marginal difference in physical functioning/health (P = 0.07). Except for a lower score in patient school functioning of patients after LTx (P = 0.01), HRQOL-results showed no difference from healthy children in any group. CONCLUSIONS The HRQOL of patients with PFIC after PEBD was similar to those after LTx. The HRQOL in both groups was also similar to that of healthy children. Thus, our data support the current policy of PEBD as primary surgical treatment for patients with PFIC without cirrhosis.
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Flores CD, Yu YR, Miloh TA, Goss J, Brandt ML. Surgical outcomes in Alagille syndrome and PFIC: A single institution's 20-year experience. J Pediatr Surg 2018; 53:976-979. [PMID: 29729773 DOI: 10.1016/j.jpedsurg.2018.02.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 02/01/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Alagille Syndrome (AGS) and Progressive Familial Intrahepatic Cholestasis (PFIC) are rare pediatric biliary disorders that lead to progressive liver disease. This study reviews our experience with the surgical management of these disorders over the last 20years. METHODS We retrospectively reviewed the records of children diagnosed with AGS or PFIC from January 1996 to December 2016. Data collected included demographics, surgical intervention (liver transplant or biliary diversion), and complications. RESULTS Of 37 patients identified with these disorders, 17 patients (8 AGS,9 PFIC) underwent surgical intervention. Mean postsurgical follow-up was 6.9±4.7years. Liver transplantation was the most common procedure (n=14). Two patients who were initially thought to have biliary atresia underwent hepatoportoenterostomy, but were subsequently shown to have Alagille syndrome. Biliary diversion procedures were performed in 3 patients (external n=1, internal n=2). PFIC patients tended to be older at the time of liver transplant compared to AGS (4.3±3.9years vs. 2.4±1.1years, p=0.25). The AGS patient with external diversion had resolution of symptoms and no complications (follow-up: 12.5years). Both PFIC patients with internal diversion (conduit between gallbladder and transverse colon) had resolution of pruritus and no progression of liver disease (follow-up: 3.8 and 4.5years). CONCLUSIONS AGS and PFIC are rare biliary disorders in children which result in pruritus and progressive liver failure. Three patients in this series (8%) benefited from biliary diversion for control of pruritus and have not to date required transplantation for progressive liver disease. 38% underwent transplantation owing to pruritus and severe liver dysfunction. LEVEL OF EVIDENCE 2b.
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Affiliation(s)
- Celia D Flores
- Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, TX, United States; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States
| | - Yangyang R Yu
- Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, TX, United States; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States
| | - Tamir A Miloh
- Section of Hepatology and Liver Transplant Medicine, Department of Pediatrics, Texas Children's Hospital, , Houston, TX, United States
| | - John Goss
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States
| | - Mary L Brandt
- Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, TX, United States; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, United States.
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Erginel B, Soysal FG, Durmaz O, Celik A, Salman T. Long-term outcomes of six patients after partial internal biliary diversion for progressive familial intrahepatic cholestasis. J Pediatr Surg 2018; 53:468-471. [PMID: 29174177 DOI: 10.1016/j.jpedsurg.2017.10.055] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2016] [Revised: 10/19/2017] [Accepted: 10/22/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Partial internal biliary diversion (PIBD) is an alternative approach for the treatment of devastating pruritus in patients with progressive familial intrahepatic cholestasis (PFIC). In these patients quality of life can be improved and progression of liver disease can be delayed while waiting for liver transplantation. The aim of our study was to evaluate six patients with PFIC who have undergone PIBD in long-term follow-up. METHODS Retrospective review of the records of six patients who underwent PIBD for PFIC between 2008 and 2010 was conducted to evaluate age, growth, clinical and laboratory studies for long-term outcome. RESULTS Serum postoperative bile acid levels were reduced from a mean 340.1μmol/L (range 851-105) preoperatively to a mean of 96.3μmol/L at postoperative fifth year. The difference between pre- and postoperative bile acid levels was statistically significant (p=0.018). AST decreased from 79.1U/L (range 43-150U/L) to 64.6U/L (range 18-172U/L), ALT decreased from 102.8U/L (range 35-270U/L) to 84.6U/L and total bilirubin decreased from 2.9μmol/L (range 0.35-6.4μmol/L) to 1.53μmol/L (range 0.3-2.4). Again, the decrease in total bilirubin levels was significant (p=0.043). Pruritus was diminished from a mean of +4 (range 4-4) preoperatively to a mean of +2 (4-0). One patient who underwent liver transplantation owing to relapsing pruritus died from postoperative sepsis in the early postoperative period at the fifth year after PBID. Five symptom-free patients have not required liver transplantation at a mean period of 6.1±0.83years (5.1-7.0years) follow-up. CONCLUSION PBID is an effective surgical procedure in the long-term and can delay the need for liver transplantation in children with PFIC by reducing jaundice and pruritus.
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Affiliation(s)
- Basak Erginel
- Istanbul University, Istanbul Medical Faculty, Department of Pediatric Surgery.
| | - Feryal Gun Soysal
- Istanbul University, Istanbul Medical Faculty, Department of Pediatric Surgery
| | - Ozlem Durmaz
- Istanbul University, Istanbul Medical Faculty, Department of Pediatric Gastroenterology
| | - Alaattin Celik
- Istanbul University, Istanbul Medical Faculty, Department of Pediatric Surgery
| | - Tansu Salman
- Istanbul University, Istanbul Medical Faculty, Department of Pediatric Surgery
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Xiang D, He J, Wang H, Xiong F, Cheng H, Ai J, Shan R, Wan R, Zhang L, Shi J. Liver transplantation for decompensated liver cirrhosis caused by progressive familial intrahepatic cholestasis type 3: A case report. Medicine (Baltimore) 2017; 96:e9158. [PMID: 29390323 PMCID: PMC5815735 DOI: 10.1097/md.0000000000009158] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
RATIONALE Progressive familial intrahepatic cholestasis (PFIC) type 3, characterized by high gamma glutamyl transferase (GGT), is an autosomal recessive genetic disease. It often occurs in patients' first years of age. However, high GGT type PFIC is still rare. PATIENT CONCERNS The present study reports a case of liver transplantation for decompensated liver cirrhosis caused by PFIC type 3. An 18-year-old male presented with a history of abdominal distension and jaundice for 2 months. He had abdominal tenderness but no rebounding pain. Moreover, his dullness was felt over the liver and the spleen was palpable 8 cm below the ribs. DIAGNOSES Computed tomography and magnetic resonance cholangiopancreato graphy of the upper abdomen revealed cirrhosis, portal hypertension, collateral circulation formation, large spleen, and ascites. Blood biochemistry showed high alanine transaminase, aspartate transaminase, and GGT. The diagnosis of decompensated liver cirrhosis caused by PFIC-3 was finally confirmed by plasma gene detecting. INTERVENTIONS The patient received an open surgery named allogeneic liver transplantation after successful matching of immune types between the recipient and donor. Peritoneal puncture and catheter drainage under B-ultrasound was performed when an encapsulated effusion between the liver and stomach arose. OUTCOMES The patient was discharged without specific discomfort and was almost free of fluid accumulation 51 days after the surgery. At the 6-month follow-up, he had no discomfort and the blood routine, liver functions showed no abnormalities. LESSONS We found a new mutant fragment of ABCB4 gene in the process of diagnosis. Liver transplantation remains the most definitive treatment for PFIC. Current medical therapies and surgical interventions such as biliary diversion have potentially created a synergistic outcome.
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Affiliation(s)
- Deng Xiang
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Jiannan He
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Hongmei Wang
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Fangfang Xiong
- Basic Nursing Teaching and Research Office, Nanchang City Health School
| | - Hao Cheng
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Junhua Ai
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Renfeng Shan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Renhua Wan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
| | - Lunli Zhang
- Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jun Shi
- Department of General Surgery, The First Affiliated Hospital of Nanchang University
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Wang KS, Tiao G, Bass LM, Hertel PM, Mogul D, Kerkar N, Clifton M, Azen C, Bull L, Rosenthal P, Stewart D, Superina R, Arnon R, Bozic M, Brandt ML, Dillon PA, Fecteau A, Iyer K, Kamath B, Karpen S, Karrer F, Loomes KM, Mack C, Mattei P, Miethke A, Soltys K, Turmelle YP, West K, Zagory J, Goodhue C, Shneider BL. Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis. Hepatology 2017; 65:1645-1654. [PMID: 28027587 PMCID: PMC5397365 DOI: 10.1002/hep.29019] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 11/21/2016] [Accepted: 12/20/2016] [Indexed: 12/12/2022]
Abstract
UNLABELLED To evaluate the efficacy of nontransplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 with Alagille syndrome (ALGS), 16 with familial intrahepatic cholestasis-1 (FIC1), 18 with bile salt export pump (BSEP) disease, and 4 others with low γ-glutamyl transpeptidase disease (levels <100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data were collected retrospectively from individuals who collectively had 39 partial external biliary diversions (PEBDs), 11 ileal exclusions (IEs), and seven gallbladder-to-colon (GBC) diversions. Serum total bilirubin decreased after PEBD in FIC1 (8.1 ± 4.0 vs. 2.9 ± 4.1 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.02), but not in ALGS or BSEP. Total serum cholesterol decreased after PEBD in ALGS patients (695 ± 465 vs. 457 ± 319 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.0001). Alanine aminotransferase levels increased in ALGS after PEBD (182 ± 70 vs. 260 ± 73 IU/L, preoperatively vs. 24 months; P = 0.03), but not in FIC1 or BSEP. ALGS, FIC1, and BSEP patients experienced less severely scored pruritus after PEBD (ALGS, 100% vs. 9% severe; FIC1, 64% vs. 10%; BSEP, 50% vs. 20%, preoperatively vs. >24 months postoperatively, respectively; P < 0.001). ALGS patients experienced a trend toward greater freedom from xanthomata after PEBD. There was a trend toward decreased pruritus in FIC1 after IE and GBC. Vitamin K supplementation increased in ALGS after PEBD (33% vs. 77%; P = 0.03). Overall, there were 15 major complications after surgery. Twelve patients (3 ALGS, 3 FIC1, and 6 BSEP) subsequently underwent liver transplantation. CONCLUSION This was a multicenter analysis of nontransplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally, although not uniformly, result in improvement of pruritus and cholestasis. (Hepatology 2017;65:1645-1654).
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Affiliation(s)
| | - Greg Tiao
- Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Lee M. Bass
- Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
| | | | | | - Nanda Kerkar
- Children’s Hospital Los Angeles, Los Angeles, CA
| | | | - Colleen Azen
- Children’s Hospital Los Angeles, Los Angeles, CA
| | - Laura Bull
- University of California, San Francisco, CA
| | | | | | | | | | - Molly Bozic
- Riley Hospital for Children, Indianapolis, IN
| | | | | | | | | | | | - Saul Karpen
- Children’s Healthcare of Atlanta, Atlanta, GA
| | | | | | - Cara Mack
- Children’s Hospital Colorado, Aurora, CO
| | - Peter Mattei
- Children’s Hospital of Philadelphia, Philadelphia, PA
| | | | - Kyle Soltys
- Children’s Hospital of Pittsburgh, Pittsburgh, PA
| | | | - Karen West
- Riley Hospital for Children, Indianapolis, IN
| | | | - Cat Goodhue
- Children’s Hospital Los Angeles, Los Angeles, CA
| | - Benjamin L. Shneider
- Texas Children’s Hospital, Houston, TX,Children’s Hospital of Pittsburgh, Pittsburgh, PA
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12
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van der Woerd WL, Houwen RHJ, van de Graaf SFJ. Current and future therapies for inherited cholestatic liver diseases. World J Gastroenterol 2017; 23:763-775. [PMID: 28223721 PMCID: PMC5296193 DOI: 10.3748/wjg.v23.i5.763] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 11/16/2016] [Accepted: 01/11/2017] [Indexed: 02/06/2023] Open
Abstract
Familial intrahepatic cholestasis (FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phenotypes range from benign recurrent intrahepatic cholestasis (BRIC), associated with recurrent cholestatic attacks, to progressive FIC (PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency (PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency (PFIC1 and PFIC2). When treatment fails, liver transplantation is needed which is associated with complications like rejection, post-transplant hepatic steatosis and recurrence of disease. Therefore, the need for more and better therapies for this group of chronic diseases remains. Here, we discuss new symptomatic treatment options like total biliary diversion, pharmacological diversion of bile acids and hepatocyte transplantation. Furthermore, we focus on emerging mutation-targeted therapeutic strategies, providing an outlook for future personalized treatment for inherited cholestatic liver diseases.
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13
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Mali VP, Fukuda A, Shigeta T, Uchida H, Hirata Y, Rahayatri TH, Kanazawa H, Sasaki K, de Ville de Goyet J, Kasahara M. Total internal biliary diversion during liver transplantation for type 1 progressive familial intrahepatic cholestasis: a novel approach. Pediatr Transplant 2016; 20:981-986. [PMID: 27534385 DOI: 10.1111/petr.12782] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/13/2016] [Indexed: 12/11/2022]
Abstract
LT for PFIC type 1 is often complicated by postoperative diarrhea and recurrent graft steatosis. A 26-month-old female child with cholestatic jaundice, pruritus, diarrhea, and growth retardation revealed total bilirubin 9.1 mg/dL, gamma-glutamyl transpeptidase 64 IU/L, and TBA 295.8 μmol/L. Genetic analysis confirmed ATP8B1 defects. A LT (segment 2, 3 graft) from the heterozygous father was performed. Biliary diversion was performed by a 35-cm jejunum conduit between the graft hepatic duct and the mid-transverse colon. Stools became pigmented immediately. Follow-up at 138 days revealed resolution of jaundice and pruritus and soft-to-hard stools (6-8 daily). Radioisotope hepato-biliary scintigraphy (days 26, 68, and 139) confirmed unobstructed bile drainage into the colon (t1/2 34, 27, and 19 minutes, respectively). Contrast meal follow-through at day 62 confirmed the absence of any colo-jejuno-hepatic reflux. At 140 days, contrast follow-through via the biliary stent revealed patent jejuno-colonic anastomosis and satisfactory transit. Graft biopsy at LT, 138 days, and 9 months follow-up revealed comparable grades of macrovesicular steatosis (<20%). TIBD during LT may be a clinically effective stoma-free biliary diversion and may prevent recurrent graft steatosis following LT for PFIC type 1.
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Affiliation(s)
- V P Mali
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
| | - A Fukuda
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - T Shigeta
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - H Uchida
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - Y Hirata
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - T H Rahayatri
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - H Kanazawa
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - K Sasaki
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
| | - J de Ville de Goyet
- Department of Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy.,Paediatric Surgery Chair, Università di Roma Tor Vergata, Rome, Italy
| | - M Kasahara
- Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
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14
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Mehl A, Bohorquez H, Serrano MS, Galliano G, Reichman TW. Liver transplantation and the management of progressive familial intrahepatic cholestasis in children. World J Transplant 2016; 6:278-290. [PMID: 27358773 PMCID: PMC4919732 DOI: 10.5500/wjt.v6.i2.278] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 02/24/2016] [Accepted: 03/14/2016] [Indexed: 02/05/2023] Open
Abstract
Progressive familial intrahepatic cholestasis (PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described.
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15
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Gunaydin M, Tander B, Demirel D, Caltepe G, Kalayci AG, Eren E, Bicakcı U, Rizalar R, Ariturk E, Bernay F. Different techniques for biliary diversion in progressive familial intrahepatic cholestasis. J Pediatr Surg 2016; 51:386-9. [PMID: 26382286 DOI: 10.1016/j.jpedsurg.2015.08.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Revised: 08/11/2015] [Accepted: 08/15/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND Progressive familial intrahepatic cholestasis (PFIC) is a cholestatic liver disease of childhood. Pruritus resulting from increased bile salts in serum might not respond to medical treatment, and internal or external biliary drainage methods have been described. In this study, we aimed to evaluate different internal drainage techniques in patients with PFIC. PATIENTS AND METHODS Between 2009 and 2014, seven children (4 male, 3 female, 3months-5years old), (median 2years of age) with PFIC were evaluated. The patients were reviewed according to age, gender, complaints, surgical technique, laboratory findings and outcome. In each two patients, cholecystoileocolonic anastomosis, cholecystojejunocolonic anastomosis and cholecystocolostomy were performed. Cholecysto-appendico-colonic anastomosis was the technique used in one patient. RESULTS Jaundice and excessive pruritus were the main complaints. One of the patients with cholecystoileocolonic anastomosis died of comorbid pathologies (cirrhosis, adhesive obstruction and severe sepsis). Temporary rectal bleeding was observed in all the patients postoperatively. Regardless of the surgical technique, pruritus was dramatically decreased in all the patients in the postoperative period. CONCLUSION Regardless of the technique, internal biliary diversion methods are beneficial for the relief of pruritus in PFIC patients. Selection of the surgical method might vary depending on the surgeon's preference and the surgical anatomy of the gastrointestinal system of the patient.
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Affiliation(s)
- Mithat Gunaydin
- Department of Pediatric Surgery, Ondokuz Mayis University, Samsun, Turkey.
| | - Burak Tander
- Department of Pediatric Surgery, Ondokuz Mayis University, Samsun, Turkey
| | - Dilek Demirel
- Department of Pediatric Surgery, Ondokuz Mayis University, Samsun, Turkey
| | - Gonul Caltepe
- Department of Pediatric Gastroenterology, Ondokuz Mayis University, Samsun, Turkey
| | - Ayhan Gazi Kalayci
- Department of Pediatric Gastroenterology, Ondokuz Mayis University, Samsun, Turkey
| | - Esra Eren
- Department of Pediatric Gastroenterology, Ondokuz Mayis University, Samsun, Turkey
| | - Unal Bicakcı
- Department of Pediatric Surgery, Ondokuz Mayis University, Samsun, Turkey
| | - Riza Rizalar
- Department of Pediatric Surgery, Ondokuz Mayis University, Samsun, Turkey
| | - Ender Ariturk
- Department of Pediatric Surgery, Ondokuz Mayis University, Samsun, Turkey
| | - Ferit Bernay
- Department of Pediatric Surgery, Ondokuz Mayis University, Samsun, Turkey
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16
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Cholecysto-appendicostomy as partial internal biliary drainage in Progressive Familial Intrahepatic Cholestasis Type 1: A case report and review of literature. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2016. [DOI: 10.1016/j.epsc.2015.11.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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17
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Ricca RL, Harting MT, Healey PJ, Javid PJ. Intussusception of bypassed ileal segment following ileal exclusion for progressive familial intrahepatic cholestasis. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2014. [DOI: 10.1016/j.epsc.2014.06.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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18
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Hepatobiliary physiological changes after Roux-en-Y cholecysto-colonic diversion. J Pediatr Surg 2014; 49:1104-8. [PMID: 24952797 DOI: 10.1016/j.jpedsurg.2014.02.041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 02/11/2014] [Accepted: 02/12/2014] [Indexed: 01/12/2023]
Abstract
BACKGROUND We speculated that Roux-en-Y cholecysto-colonic diversion was as effective for treating children with progressive familial intrahepatic cholestasis (PFIC) as partial biliary diversion. The feasibility of the novel approach in bypassing bile was investigated in rabbits. METHODS Twenty-four rabbits were randomly divided into three groups: sham operated group (Group1), 30cm limb group (Group 2), and 10 cm limb group (Group 3). Group 2 or 3 underwent a Roux-en-Y cholecystocolonic anastomoses with a 30- or 10-cm-long Roux limb. (99mTc)EHIDA dynamic biligraphy was used to detect alterations of bile flow among the three groups at 1 year postoperatively. TBA levels and histological changes were also evaluated. RESULTS All animals survived and developed normally without clinical symptoms during 1 year follow-up. Bile was diverted into colon directly after cholecystocolonic anastomosis. In group 3, E20 and E35 values were (77.27 ± 6.15%) and (90.39 ± 1.49%) respectively. Gallbladder emptying was accelerated in 10 cm short limb group than in 30 cm long limb group. The ratio of bile shunt was (0.547 ± 0.182), which was also more than that in group 2 (p<0.05). The activity-time curve for the gallbladder area in group 2 looks like a wave. A significant reduction in TBA level was observed in group 2 and 3 (p<0.05). CONCLUSIONS Roux-en-Y cholecystocolonic bypass was safe and feasible. Its effectiveness is related to the length of Roux loop. Cholecystocolonic bypass led to a significant loss of bile acids in healthy rabbits and might be considered for bile diversion in pediatric patients with selected cholestatic diseases.
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19
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Laparoscopic cholecystocolostomy: a novel surgical approach for the treatment of progressive familial intrahepatic cholestasis. Ann Surg 2014. [PMID: 23187749 DOI: 10.1097/sla.0b013e31827905eb] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Conventionally, liver transplantation, ileoileal bypass, and partial external or internal biliary diversion are used in the treatment of progressive familial intrahepatic cholestasis (PFIC). However, postoperative recurrence, chronic diarrhea, and permanent stoma are the major concerns. We present a novel approach of laparoscopic cholecystocolostomy with antireflux Y-loop for the management of children with PFIC. METHODS Between August 2003 and April 2011, 20 children with PFIC (median age: 1.47 years; range: 10.8 months to 5.11 years) successfully underwent laparoscopic cholecystocolostomies for bile diversions. Gallbladder was incised longitudinally for cholecystocolostomy. Transverse colon was divided proximal to splenic flexure. End-to-side anastomosis was established between distal transverse colon and mid-descending colon. The mobilized splenic flexure and proximal descending colon, that is, the stem of the Y-loop, was anastomosed to the gallbladder. RESULTS The mean operative time was 2.02 ± 0.18 hours (range: 2-2.5 hours). The mean postoperative hospital stay was 8 days (range: 5-10 days). Average time for full resumption of diet was 3 days (range: 2-4 days). Average Y-loop length was 17.65 cm (range: 15-20 cm). The median follow-up period was 54 months (range: 12-104 months). All patients were jaundice free after 7 to 20 days and pruritus subsided in 3 to 14 days. Liver function parameters significantly improved postoperatively. Success rate (normalization of serum bile acids at postoperative 12 months) was 85%. No mortality or morbidities associated with diarrhea, cholangitis, or intrahepatic reflux were observed. CONCLUSIONS The novel approach of laparoscopic cholecystocolostomy offers a safe and effective treatment option for PFIC in children with good success rates and minimal morbidity.
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20
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Sheflin-Findling S, Arnon R, Lee S, Chu J, Henderling F, Kerkar N, Iyer K. Partial internal biliary diversion for Alagille syndrome: case report and review of the literature. J Pediatr Surg 2012; 47:1453-6. [PMID: 22813814 DOI: 10.1016/j.jpedsurg.2012.04.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2012] [Revised: 03/29/2012] [Accepted: 04/15/2012] [Indexed: 11/26/2022]
Abstract
This is a case report of the first patient with Alagille syndrome (AGS) to undergo a partial internal biliary diversion (PIBD) for the treatment of symptoms refractory to medical therapy. Alagille syndrome is a hereditary disease resulting in chronic cholestasis and hypercholesterolemia that can lead to severe and intractable pruritus and disfiguring and debilitating xanthomas. PIBD has proven to be an effective treatment option for other causes of cholestatic liver disease. This report reviews the immediate and 2-year follow-up of a patient after this surgical procedure. The results suggest that PIBD has potential to provide relief of intractable symptoms and improve the quality of life in patients with AGS while avoiding an external stoma. It does not, however, appear to prevent the progression of liver disease. Long-term follow-up is still needed.
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Affiliation(s)
- Shari Sheflin-Findling
- Division of Pediatric Gastroenterology, Mount Sinai Medical Center, New York, NY 10029, USA.
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21
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Mochizuki K, Obatake M, Takatsuki M, Nakatomi A, Hayashi T, Okudaira S, Eguchi S. Partial internal biliary diversion for patients with progressive familial intrahepatic cholestasis type 1. Pediatr Surg Int 2012; 28:51-4. [PMID: 22033772 DOI: 10.1007/s00383-011-3018-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
We herein report a case of progressive familial intrahepatic cholestasis with partial internal biliary diversion (PIBD). Although by using PIBD an external stoma can be avoided, exposure of the ileocecal junction to bile reflux as well as the effects of the direct bile flow on the colonic mucosa require further investigation.
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Affiliation(s)
- Kyoko Mochizuki
- Division of Pediatric Surgery, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
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El-Shabrawi MHF, Kamal NM. Medical management of chronic liver diseases (CLD) in children (part II): focus on the complications of CLD, and CLD that require special considerations. Paediatr Drugs 2011; 13:371-83. [PMID: 21999650 DOI: 10.2165/11591620-000000000-00000] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Treatment of the causes of many chronic liver diseases (CLDs) may not be possible. In this case, complications must be anticipated, prevented or at least controlled by the best available therapeutic modalities. There are three main goals for the management of portal hypertension: (i) prevention of the first episode of variceal bleeding largely by non-selective β-adrenoceptor antagonists, which is not generally recommended in children; (ii) control of bleeding by using a stepwise approach from the least to most invasive strategies; (iii) and prevention of re-bleeding using bypass operations, with particular enthusiasm for the use of meso-Rex bypass in the pediatric population. Hepatic encephalopathy management also consists of three main aspects: (i) ruling out other causes of encephalopathy; (ii) identifying and treating precipitating factors; and (iii) starting empiric treatment with drugs such as lactulose, rifaximin, sodium benzoate, and flumazenil. Treatment of mild ascites and peripheral edema should begin with the restriction of sodium and water, followed by careful diuresis, then large-volume paracentesis associated with colloid volume expansion in severe cases. Empiric broad spectrum antimicrobial therapy should be used for the treatment of spontaneous bacterial peritonitis, bacterial and fungal sepsis, and cholangitis, after taking appropriate cultures, with appropriate changes in therapy after sensitivity testing. Empirical therapies continue to be the standard practice for pruritus; these consist of bile acid binding agents, phenobarbital (phenobarbitone), ursodeoxycholic acid, antihistamines, rifampin (rifampicin), and carbamazepine. Partial external biliary diversion can be used in refractory cases. Once hepatorenal syndrome is suspected, treatment should be initiated early in order to prevent the progression of renal failure; approaches consist of general supportive measures, management of concomitant complications, screening for sepsis, treatment with antibiotics, use of vasopressin analogs (terlipressin), and renal replacement therapy if needed. Hepatopulmonary syndrome and portopulmonary hypertension are best managed by liver transplantation. Provision of an adequate caloric supply, nutrition, and vitamin/mineral supplements for the management of growth failure, required vaccinations, and special care for ensuring psychologic well-being should be ensured. Anticoagulation might be attempted in acute portal vein thrombosis. Some CLDs, such as extrahepatic biliary atresia (EHBA), Crigler-Najjar syndrome, and Indian childhood cirrhosis, require special considerations. For EHBA, Kasai hepatoportoenterostomy is the current standard surgical approach in combination with nutritional therapy and supplemental fat and water soluble vitamins, minerals, and trace elements. In type 1 Crigler-Najjar syndrome, extensive phototherapy is the mainstay of treatment, in association with adjuvant therapy to bind photobilirubin such as calcium phosphate, cholestyramine, or agar, until liver transplantation can be carried out. Treating Indian childhood cirrhosis with penicillamine early in the course of the disease and at doses similar to those used to treat Wilson disease decreases the mortality rate by half. New hopes for the future include extracorporeal liver support devices (the molecular adsorbent recirculating system [MARS®] and Prometheus®), hepatocyte transplantation, liver-directed gene therapy, genetically engineered enzymes, and therapeutic modalities targeting fibrogenesis. Hepapoietin, a naturally occurring cytokine that promotes hepatocyte growth, is under extensive research.
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