Total Parenteral Nutrition induced Liver Pathology: An Autopsy Series of 24 Newborn Cases
Tóm tắt
Total parenteral nutrition (TPN)-induced liver injury is a common complication in neonates managed with newborn intensive care. In several of these cases, irreversible and even fatal liver damage may develop, with patients dying of liver failure. In spite of multiple studies over several years, the pathogenesis of TPN-induced liver damage remains poorly understood. Clinical data from 24 neonates with clinical history of receiving TPN who died at Yale—New Haven Children’s Hospital and had autopsies performed, were collected by medical record review without knowledge of liver pathology findings. Liver histological sections from these patients were evaluated for multiple parameters without knowledge of the clinical course. Continuous data were analyzed by Wilcoxon signed-rank test and Mann-Whitney test, and dichotomous data by Fisher’s exact test; P < 0.05 was considered significant. Different histopathological abnormalities with varying degrees of severity were observed. A progression in the severity of histopathological changes in relation to duration of TPN administration (DTPN) was found. While patients with DTPN of < 2 wk had no fibrosis or only mild degrees of fibrosis, patients with more than 6 wk of DTPN developed moderate-to-severe fibrosis. Similar results were observed for cholestasis and bile duct proliferation. We did not find significant differences for birth weight, gestational age, occurrence of necrotizing enterocolitis, sepsis, or enteral feedings between the group with normal-to-mild liver changes (n = 16), and the group with moderate-to-severe liver changes (n = 8). On the other hand, DTPN was significantly different between these two groups (P = 0.008). Also, patients small for gestational age (P = 0.003) and patients with bronchopulmonary dysplasia (P = 0.001) were more commonly seen in the group with moderate-to-severe histopathological findings. Intracellular copper was detected in 12.5% of patients with moderate-to-severe liver changes, and was found in 50% of patients with normal-to-mild liver findings (P = 0.04). Detection of copper from tissue sections also decreased with DTPN, being observed in 57% of patients with < 2 wk DTPN and in none of the patients with > 12 wk DTPN. Our findings confirm the known significant relationship between the duration of TPN and liver injury. While previously described associations with birth weight, gestational age, enteral feedings, necrotizing enterocolitis, and sepsis were not noted, our study suggests that poor intrauterine growth may be a significant clinical risk factor for TPN-induced liver injury. In addition, our findings suggest that copper may have a protective effect against the development of TPN-induced liver damage.
Tài liệu tham khảo
DA Kelly (1998) ArticleTitleLiver complications of pediatric parenteral nutrition—epidemiology Nutrition 14 153–157 Occurrence Handle1:STN:280:DyaK1c7gtVemtA%3D%3D Occurrence Handle10.1016/S0899-9007(97)00232-3 Occurrence Handle9437702
EF Beale et al. (1979) ArticleTitleIntrahepatic cholestasis associated with parenteral nutrition in premature infants Pediatrics 64 342–347 Occurrence Handle1:STN:280:DyaL3c%2Fht1Gqsg%3D%3D Occurrence Handle113770
R Rager MJ Finegold (1975) ArticleTitleCholestasis in immature newborn infants: is parenteral alimentation responsible J Pediatr 86 264–269 Occurrence Handle1:STN:280:DyaE2M%2FptFersA%3D%3D Occurrence Handle10.1016/S0022-3476(75)80486-0 Occurrence Handle803386
DR Benjamin (1981) ArticleTitleHepatobiliary dysfunction in infants and children associated with long-term total parenteral nutrition. A clinico-pathologic study Am J Clin Pathol 76 276–283 Occurrence Handle1:STN:280:DyaL38%2FitFSisA%3D%3D Occurrence Handle10.1093/ajcp/76.3.276 Occurrence Handle6792901
RJ Merritt (1986) ArticleTitleCholestasis associated with total parenteral nutrition J Pediatr Gastroenterol Nutr 5 9–22 Occurrence Handle1:STN:280:DyaL287hsVKjsg%3D%3D Occurrence Handle10.1097/00005176-198601000-00004 Occurrence Handle3080580
FG Mullick CA Moran KG Ishak (1994) ArticleTitleTotal parenteral nutrition: ahistopathologic analysis of the liver changes in 20 children Mod Pathol 7 190–194 Occurrence Handle1:STN:280:DyaK2c3nsl2ktw%3D%3D Occurrence Handle8008742
ER Briones FL Iber (1995) ArticleTitleLiver and biliary tract changes and injury associated with total parenteral nutrition: pathogenesis and prevention J Am Coll Nutr 14 219–228 Occurrence Handle1:STN:280:DyaK287ntlWitg%3D%3D Occurrence Handle10.1080/07315724.1995.10718499 Occurrence Handle8586769
EM Quigley et al. (1993) ArticleTitleHepatobiliary complications of total parenteral nutrition Gastroenterology 104 286–301 Occurrence Handle1:STN:280:DyaK3s7it1CltA%3D%3D Occurrence Handle10.1016/0016-5085(93)90395-S Occurrence Handle8419252
SV Beath et al. (1996) ArticleTitleParenteral nutrition-related cholestasis in postsurgical neonates: multivariate analysis of risk factors J Pediatr Surg 31 604–606 Occurrence Handle1:STN:280:DyaK283nt1CjtA%3D%3D Occurrence Handle10.1016/S0022-3468(96)90507-2 Occurrence Handle8801324
GL Klein et al. (1984) ArticleTitleHepatic aluminum accumulation in children on total parenteral nutrition J Pediatr Gastroenterol Nutr 3 740–743 Occurrence Handle1:STN:280:DyaL2M%2FlslGjtg%3D%3D Occurrence Handle10.1097/00005176-198411000-00018 Occurrence Handle6438295
D Bougle et al. (1993) ArticleTitleChromium and parenteral nutrition in children J Pediatr Gastroenterol Nutr 17 72–74 Occurrence Handle1:STN:280:DyaK3szltlentw%3D%3D Occurrence Handle10.1097/00005176-199307000-00010 Occurrence Handle8350214
KE Bove et al. (1995) ArticleTitleVasculopathic hepatotoxicity associated with E-Ferol syndrome in low-birth-weight infants JAMA 254 2422–2430 Occurrence Handle10.1001/jama.1985.03360170062032
AP Reynolds E Kiely N Meadows (1994) ArticleTitleManganese in long term paediatric parenteral nutrition Arch Dis Child 71 527–528 Occurrence Handle1:STN:280:DyaK2M3ktlKqtA%3D%3D Occurrence Handle10.1136/adc.71.6.527 Occurrence Handle7726613 Occurrence Handle1030090
JM Fell et al. (1996) ArticleTitleManganese toxicity in children receiving long-term parenteral nutrition Lancet 347 1218–1221 Occurrence Handle1:STN:280:DyaK283gs1Ciug%3D%3D Occurrence Handle10.1016/S0140-6736(96)90735-7 Occurrence Handle8622451
MR Brown et al. (1989) ArticleTitleDecreased cholestasis with enteral instead of intravenous protein in the very low-birth-weight infant J Pediatr Gastroenterol Nutr 9 21–27 Occurrence Handle1:STN:280:DyaL1MzotF2mtg%3D%3D Occurrence Handle10.1097/00005176-198909010-00005 Occurrence Handle2506323
A Cooper et al. (1984) ArticleTitleTaurine deficiency in the severe hepatic dysfunction complicating total parenteral nutrition J Pediatr Surg 19 462–466 Occurrence Handle1:STN:280:DyaL2M%2FgvFaisw%3D%3D Occurrence Handle10.1016/S0022-3468(84)80276-6 Occurrence Handle6434724
R Postuma CL Trevenen (1979) ArticleTitleLiver disease in infants receiving total parenteral nutrition Pediatrics 63 110–115 Occurrence Handle1:STN:280:DyaE1M7nvFCrug%3D%3D Occurrence Handle108658
RT Stanko et al. (1987) ArticleTitleDevelopment of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition Gastroenterology 92 197–202 Occurrence Handle1:STN:280:DyaL2s%2FlsFSquw%3D%3D Occurrence Handle10.1016/0016-5085(87)90859-6 Occurrence Handle3096806
RJ Touloukian JH Seashore (1975) ArticleTitleHepatic secretory obstruction with total parenteral nutrition in the infant J Pediatr Surg 10 353–360 Occurrence Handle1:STN:280:DyaE2M7ptFentQ%3D%3D Occurrence Handle10.1016/0022-3468(75)90098-6 Occurrence Handle806674
C Cohen MM Olsen (1981) ArticleTitlePediatric total parenteral nutrition. Liver histopathology Arch Pathol Lab Med 105 152–156 Occurrence Handle1:STN:280:DyaL3M7jt1OqtA%3D%3D Occurrence Handle6781446
RJ Cooke PF Whitington D Kelts (1984) ArticleTitleEffect of taurine supplementation onhepatic function during short-term parenteral nutrition in the premature infant J Pediatr Gastroenterol Nutr 3 234–238 Occurrence Handle1:CAS:528:DyaL2cXitVygsr8%3D Occurrence Handle10.1097/00005176-198403000-00012 Occurrence Handle6423796
RL Moss JB Das JG Raffensperger (1996) ArticleTitleNecrotizing enterocolitis and total parenteral nutrition-associated cholestasis Nutrition 12 340–343 Occurrence Handle1:STN:280:DyaK2s%2FivFGjug%3D%3D Occurrence Handle10.1016/S0899-9007(96)80057-8 Occurrence Handle8875518
RS Britton (1996) ArticleTitleMetal-induced hepatotoxicity Semin Liver Dis 16 3–12 Occurrence Handle1:STN:280:DyaK28zgtVKisw%3D%3D Occurrence Handle10.1055/s-2007-1007214 Occurrence Handle8723319
MM Pena J Lee DJ Thiele (1999) ArticleTitleA delicate balance: homeostatic control of copper uptake and distribution J Nutr 129 1251–1260 Occurrence Handle1:CAS:528:DyaK1MXkt12nt7Y%3D Occurrence Handle10395584
G Bruckmann SG Zondek (1939) ArticleTitleIron, copper, and manganese in human organs at various ages Biochem J 1939 33 1845–1857 Occurrence Handle1:CAS:528:DyaH3cXitFOmsA%3D%3D
J Evans S Newman S Sherlock (1978) ArticleTitleLiver copper levels in intrahepatic cholestasis of childhood Gastroenterology 75 875–878 Occurrence Handle1:CAS:528:DyaE1MXjslejsg%3D%3D Occurrence Handle700330
G Faa et al. (1987) ArticleTitleUneven copper distribution in the human newborn liver Hepatology 7 838–842 Occurrence Handle1:CAS:528:DyaL2sXlvFGmtbg%3D Occurrence Handle10.1002/hep.1840070508 Occurrence Handle2443435
I Tulikoura E Vuori (1986) ArticleTitleEffect of total parenteral nutrition on the zinc, copper, and manganese status of patients with catabolic disease Scand J Gastroenterol 21 421–427 Occurrence Handle1:STN:280:DyaL283mtFKjtA%3D%3D Occurrence Handle10.3109/00365528609015157 Occurrence Handle3088719
JT Karpel VH Peden (1972) ArticleTitleCopper deficiency in long-term parenteral nutrition J Pediatr 80 32–36 Occurrence Handle1:STN:280:DyaE387ltlOmsQ%3D%3D Occurrence Handle10.1016/S0022-3476(72)80449-9 Occurrence Handle4622715
RC Benyon MJ Arthur (1998) ArticleTitleMechanisms of hepatic fibrosis J Pediatr Gastroenterol Nutr 27 75–85 Occurrence Handle1:CAS:528:DyaK1cXksFSjsLk%3D Occurrence Handle10.1097/00005176-199807000-00013 Occurrence Handle9669730