Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study.

OBJECTIVE: To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS: Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS: FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.

Survival outcomes of pediatric intestinal failure patients: analysis of factors contributing to improved survival over the past two decades.

BACKGROUND: Intestinal failure (IF) is associated with significant and life-threatening complications. Recent studies suggest that treatments for IF in the pediatric population are improving over time. Based on this, we examined whether pediatric IF survival rates have improved in our patient population over the past two decades, and secondarily examined which aspects of patient care contributed to changes in survival. METHODS: We conducted a retrospective chart review of all pediatric patients with IF at our children's hospital from 1990 through 2009. Cox regression analyses were used to determine change in survival rates over time (5-y cohorts), and we examined multiple covariates to determine their potential influence on survival rates over time. RESULTS: A significant improvement in survival of 171 children with IF was noted over the past two decades. Children with an onset of IF in the 1990-1994 cohort had significantly decreased survival compared with children in all subsequent cohorts (P = 0.011). The only intervention that was identified between this time period and future periods was the establishment of a comprehensive intestinal failure clinical care team. While the latter three cohorts were not significantly different, progressively increased survival was noted. Ability to wean off parenteral nutrition (PN) and small bowel length greater than 10% of the expected length were significantly associated with improved survival over this time period (P < 0.01). Other tested covariates, including the more recent use of ethanol lock therapy (to prevent catheter sepsis) and lipid reduction strategies (to treat PN-associated cholestasis) failed to show a significant impact on improved survival. CONCLUSIONS: Despite a striking improvement in survival of children with IF over the past two decades, the only identified intervention that significantly impacted survival was establishment of a comprehensive care team. These findings emphasize the need for multi-disciplinary efforts to care for such complex and challenging children.

Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease.

BACKGROUND: Parenteral nutrition-associated liver disease can be a progressive and fatal entity in children with short-bowel syndrome. Soybean-fat emulsions provided as part of standard parenteral nutrition may contribute to its pathophysiology. METHODS: We compared safety and efficacy outcomes of a fish-oil-based fat emulsion in 18 infants with short-bowel syndrome who developed cholestasis (serum direct bilirubin level of > 2 mg/dL) while receiving soybean emulsions with those from a historical cohort of 21 infants with short-bowel syndrome who also developed cholestasis while receiving soybean emulsions. The primary end point was time to reversal of cholestasis (3 consecutive measurements of serum direct bilirubin level of < or = 2 mg/dL). RESULTS: Among survivors, the median time to reversal of cholestasis was 9.4 and 44.1 weeks in the fish-oil and historical cohorts, respectively. Subjects who received fish-oil-based emulsion experienced reversal of cholestasis 4.8 times faster than those who received soybean emulsions and 6.8 times faster in analysis adjusted for baseline bilirubin concentration, gestational age, and the diagnosis of necrotizing enterocolitis. A total of 2 deaths and 0 liver transplantations were recorded in the fish-oil cohort and 7 deaths and 2 transplantations in the historical cohort. The provision of fish-oil-based fat emulsion was not associated with essential fatty acid deficiency, hypertriglyceridemia, coagulopathy, infections, or growth delay. CONCLUSIONS: Parenteral fish-oil-based fat emulsions are safe and may be effective in the treatment of parenteral nutrition-associated liver disease.

Can we do away with PTBD?

Percutaneous Transhepatic Biliary Drainage (PTBD) is performed in surgical jaundice to decompress the biliary tree and improve hepatic functions. However, the risk of sepsis is high in these patients due to immunosuppression and surgical outcome remains poor. This raises a question--can we do away with PTBD? To answer this query a study was carried out in 4 groups of patients bearing in mind the high incidence of sepsis and our earlier studies, which have demonstrated immunotherapeutic potential of Tinospora cordifolia (TC): (A) those undergoing surgery without PTBD (n = 14), (B) those undergoing surgery after PTBD (n = 13). The mortality was 57.14% in Group A as compared to 61.54% in Group B. Serial estimations of bilirubin levels carried out during the course of drainage (3 Wks) revealed a gradual and significant decrease from 12.52 +/- 8.3 mg% to 5.85 +/- 3.0 mg%. Antipyrine half-life did not change significantly (18.35 +/- 4.2 hrs compared to basal values 21.96 +/- 3.78 hrs). The phagocytic and intracellular killing (ICK) capacities of PMN remained suppressed (Basal: 22.13 +/- 3.68% phago. and 19.1 +/- 4.49% ICK; Post drainage: 20 +/- 8.48% Phago and 11.15 +/- 3.05% ICK). Thus PTBD did not improve the metabolic capacity of the liver and mortality was higher due to sepsis. Group (C) patients received TC during PTBD (n = 16) and Group (D) patients received TC without PTBD (n = 14). A significant improvement in PMN functions occurred by 3 weeks in both groups (30.29 +/- 4.68% phago, 30 +/- 4.84% ICK in Group C and 30.4 +/- 2.99% phago, 27.15 +/- 6.19% ICK in Group D). The mortality in Groups C and D was 25% and 14.2% respectively during the preoperative period. There was no mortality after surgery. It appears from this study that host defenses as reflected by PMN functions play an important role in influencing prognosis. Further decompression of the biliary tree by PTBD seems unwarranted.

[Biliary intervention for malignant obstructive jaundice. Treatment through PTCD fistula].

Currently, diagnosis of obstructive jaundice has become easier with CT and USEG, and percutaneous transhepatic cholangio -drainage (PTCD) for obstructive jaundice has also become much safer using USEG control. We have performed PTCD in 277 cases, from December 1976 to May 1989 at Saitama Cancer Center with specially designed thin needle. And using a PTCD fistula, we have been attempted radiotherapy for 7 cases of the bile duct cancer using Remote After Loading System (RALS), and hyperthermia for 5 cases of bile duct cancer using antenna of microwaves. From autopsy cases, we evaluated treated lesion pathologically, and we obtained the following results. Dosage of biliary RALS need up to 50 Gy at the point of 1 cm from 60Co ++source. Biliary hyperthermia using microwave seem to be unsuccessful, and further improvement to the antenna of microwave were necessary. Furthermore, we have attempted biliary endoprosthesis 27 cases, for better quality of life to the patients with malignant obstructive jaundice. These method seems to be effective in prolonging patient's lives, comparing of cases in which PTCD of an external fistula has been performed.