Ursodeoxycholic acid therapy in children with cholestatic liver disease

The beneficial effect of ursodeoxycholic add have been documented in adults but experience with this agent is limited in the pediatric population. The objective of this study was to evaluate ursodeoxycholic acid treatment in children with cholestatic liver disease. Twenty-four patients with intrahepatic cholestasis (neonatal hepatitis 7, Byler disease 7, idiopathic intrahepatic cholestasis 10) whose ages ranged from 1.5 months to 15 years were treated with ursodeoxycholic acid (15-20 mg/kg/day) for 12 months. Liver biopsy was performed initially on all patients and on 17 at the end of the twelve months. The outcome was evaluated by monitoring clinical and biochemical markers of cholestasis, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol, total serum tasting bile acids and total and conjugated bilirubin at entry and every three months of treatment. Pruritus was ameliorated in all patients; there was complete disappearance of itching in 16.7 percent. There were significant decreases in mean serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and gamma-glutamyl transpeptidase. Liver biopsy specimens showed a significant improvement in the cholestasis but not in fibrosis. No adverse effects of therapy were noted. The improvements in the clinical and biochemical parameters and tolerability of the drug suggest that ursodeoxycholic acid is a safe and effective treatment in children with intrahepatic cholestasis.     

Serum gamma-glutamyl transpeptidase activity and urinary D-glucaric acid excretion in newborns in the first week of life. Effects of phenobarbital and nicethamide combination.

High serum gamma-glutamyl transpeptidase activity was found in cord blood of newborn boys. This activity decreased to lower values on the 4th and 7th days. In newborns treated for 3 days following the birth with a combination of phenobarbital and nicethamide an increase of gamma-glutamyl transpeptidase activity occurred from the 4th to the 7th days. The 7th day levels were significantly higher when compared with the controls. Simultaneous determination of urinary glucaric acid excretion confirmed the induction of hepatic microsomal enzymes in glucuronic acid pathway. This could also be demonstrated by a pronounced decrease of serum bilirubin levels in groups receiving the enzyme inducers whether phenobarbital was administered intramuscularly or orally as sodium salt solution.     

Phototherapy and neonatal liver function.

Two groups of 'healthy' full-term infants with hyperbilirubinemia exposed to phototherapy for 72 h demonstrated no significant change in serum glutamic pyruvic transaminase (SGPT), isocitric dehydrogenase (SICD), alkaline phosphatase (SAP), heat stable alkaline phosphatase (HSAP), total protein and albumin values; these values were similar to those of a comparable group of control infants without hyperbilirubinemia. The bilirubin levels, however, decreased significantly during this period. In a separate group of full-term infants with hyperbilirubinemia, the bromsulphalein (BSP) test before and after 72 h of phototherapy also demonstrated no signficant alteration; the results were comparable to a control group of infants. Phototherapy, even for a duration of 72 h apparently does not seem to affect liver function in infants with hyperbilirubinemia.     

Kasai术后生存12年以上患儿的随访

目的 对Kasai术后长期生存者进行随访,了解其生活质量、生理发育和肝功能情况.方法 1989年3月至1997年3月对92例胆道闭锁患儿行Kasai术,对术后存活12年以上并得到随访的23例患儿,进行身高、体重、第二性征等生理发育的评价,以及肝功能、肝脏和门静脉的影像学检查.结果 23例患儿中21例进行门诊复查,2例进行信访和电话复查.21例门诊复查患儿均测量身高和体重,有4例患儿身高低于同年龄同性别参照人群身高的均值,体重则均不低于同性别、同身高参照人群体重的均值-1SD.对21例的性征发育情况进行调查,10例14岁以上男性患儿,阴茎已发育9例,9例中出现遗精4例.女性9例中,5例在15岁以前月经初潮.21例肝功能检查,16例胆红素在正常范围内,白蛋白低于正常值1例,谷丙转氨酶升高7例.血常规检查正常范围的16例,红细胞、白细胞和血小板低于正常值2例.15例患儿超声检查13例有肝硬化改变.结论 ①Kasai手术后虽然仅有小部分(23/92)的患儿存活10年以上,存活者能与正常儿童一样上学读书;②与正常同龄儿相比,患儿远期生长发育还是受一定的影响,男孩的体格生长迟缓比例较高,青春发育延迟.女孩的生长发育和性征发育则无明显延迟;③术后应定期对血清肝功能及肝脏和门静脉包括影像学的检查;④Kasai手术后远期有部分患儿需行肝移植.     

Biliary atresia recent insight

Biliary atresia (BA) is a rare disease characterized by ascending obstruction of bile ducts that exclusively affects newborn infants. The etiology of the disease is not known. BA is considered to be a phenotype resulting from several pathogenic processes leading to obstruction of the biliary tree. It usually presents shortly after birth, characterized by persistent jaundice, hepatosplenomegaly, clay-colored stool, and dark urine. It affects both the extra-hepatic biliary ducts (EHBDs) and the intra-hepatic biliary system (IHBDs), but the former is more severely affected. Diagnosis of BA is a great challenge and must be achieved as early as possible to delay progression to cirrhosis. Laboratory tests reveal direct hyperbilirubinemia and, variable levels of transaminases, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP), which overlap significantly with other causes of neonatal cholestasis. The intraoperative cholangiogram is considered the gold standard for the diagnosis of BA and is performed routinely in many institutions. BA can be divided into correctable and non-correctable types; the former accounts for (10–15%) of cases, in which the proximal common hepatic duct is patent, allowing primary anastomosis of the EHBDs to the bowel. All patients are subjected to identical surgical and medical treatments; consisting of Kasai portoenterostomy (KPE), which entails removal of the atretic extra-hepatic tissue and a Roux-en-Y jejunal loop anastomosed to the hepatic hilum. Kasai portoenterstomy is considered a transition to liver transplantation, as the pathology may be still ongoing. BA is the most frequent indication for liver transplantation in infants, which is the only treatment that can definitively arrest the natural disease course. In conclusion: BA is a serious liver disease that needs to be further studied, and awareness of BA should be increased among the public and health care workers to prevent the complications of this disease.     

Blood chemistry of normal human fetuses at midtrimester of pregnancy

Thirteen biochemical parameters and five enzymatic activities were determined on sera of 63 normal human fetuses sampled by direct puncture under ultrasound guidance, between the 20th and the 26th wk of gestation, and on their mothers. They were referred to us for various prenatal diagnoses but were well and confirmed healthy at birth. Some parameters were found to be very similar in both groups, mainly creatinine, calcium, creatine kinase, aspartate aminotransferase, and gamma-glutamyl transferase. Some values were significantly higher in the fetuses, such as total bilirubin, direct bilirubin, phosphorus, lactic dehydrogenase and alkaline phosphatase activities, and alpha-fetoprotein. Urea, uric acid, glucose, triglycerides, cholesterol, total protein, and albumin levels were found to be lower in fetuses. These data indicate a slower metabolism in fetuses compared to their mothers, a lower level of energy requirement, and a relative liver immaturity. These normal values of fetal biochemistry will improve our knowledge of physiology and help to determine the specific values of a test in fetal pathology.     

Perinatal hypoxia and hepatic cell function in preterm and full term newborn infants

Gamma-glutamyl transpeptidase activity and the serum concentration of lipoprotein-x, indirect bilirubin and total bile acids were measured in 28 preterm and 24 full term newborn infants, with or without hypoxia, at the postnatal age 3-4 days. Those preterm and full term babies who suffered from hypoxia had increased mean lipoprotein-x, bilirubin, total bile acid concentration and gamma-glutamyl transpeptidase activity in comparison to that of controls, but the differences were not significant statistically. Clinical implications of the results are briefly discussed.     

Long-term survival after Kasai's operation for biliary atresia

Long-term survival of biliary atresia patients after Kasai hepaticoportoenterostomy is being increasingly reported. Prognostic factors indicative of a favorable long-term outcome consist of: (1) early age at operation; (2) bilirubin excretion of at least 6 mg daily 1 month after operation; (3) favorable hepatic histology at the time of operation; and (4) low incidence of postoperative cholangitis. Jaundice-free long-term survival is now attained in from one-fourth to one-third of patients undergoing Kasai hepaticoportoenterostomy by experienced surgeons in the Western hemisphere. In many long-term survivors there is normalization of liver function, improvement in hepatic histology, and resolution of the complications of portal hypertension. Most patients in this category have made a normal adjustment to their disease and lead active adolescent and adult lives. Offprint requests to: B. A. Stewart     

Differentiation between extrahepatic and intrahepatic cholestasis by discriminant analysis

Discriminant analysis was used to differentiate between extrahepatic biliary atresia and intrahepatic cholestasis. Among the ten laboratory variables tested, three (gamma-glutamyl transpeptidase, alkaline phosphatase and total serum bilirubin) were useful in the differential diagnosis. gamma-Glutamyl transpeptidase contributed most to the discrimination (85%). From a population study of 28 babies with extrahepatic biliary atresia and 24 infants with intrahepatic cholestasis, the procedure achieved a diagnostic accuracy and specificity of 92.9% and an efficiency of 92.3%. The jackknife procedure has also confirmed that the mathematical model was robust for discriminant analysis and therefore it may be valid for screening infants with cholestasis for early surgical intervention. Discriminant analysis is a useful adjunct for differentiation between intrahepatic cholestasis and extrahepatic biliary atresia.     

Early predictors of success of Kasai operation in children with biliary atresia.

AIM: Aim of the study was the evaluation of early predictive parameters of event-free survival (not listed for liver transplantation, not transplanted, no death) in children suffering from biliary atresia after hepatoportoenterostomy (Kasai procedure) in order to optimize pretransplant management. PATIENTS AND METHODS: Sixty-seven infants were treated with the Kasai operation at our institution over a 20-year period from 1978 until 1998. Median age at time of operation was 51 days after birth (range 19 - 180 days). Of these 67 infants, 24 children with complete datasets and an observation time of at least one year were evaluated retrospectively using a Cox regression model. The response variable was event-free survival after a median observation time of 4.9 years (1.11- 10.37 years). Six variables were entered as covariates: alanine aminotransferase (ALAT), cholinesterase activity, bilirubin, age at the time of Kasai operation and tracer excretion and uptake during hepatobiliary scintigraphy (HBSS). All variables were evaluated six weeks after operation. For subsequent cut-off determination, a receiver operating analysis (ROC analysis) was carried out. RESULTS: Tracer excretion shown by HBSS showed the highest prognostic power to predict event-free survival after Kasai operation (log rank 18.68, p < 0.0001) followed by bilirubin and ALAT as further significant parameters in the first univariate step of the Cox regression model. In the subsequent multivariate step, the prognostic power of HBSS was improved only by bilirubin (log rank 24.6, p < 0.0001). The ROC analysis determined a cut-off for bilirubin concentrations of 57 micromol/l for event-free survival with a sensitivity of 80 % and a specificity of 78.6 %. The five-year event-free survival-rate was 100 % in the group with good tracer excretion and a bilirubin concentration of 57 micromol/l and 27 % for the other group (log rank test, p < 0. 0001). CONCLUSION: Early predictors of success of the Kasai operation in children with biliary atresia are free tracer excretion as shown by HBSS and a serum bilirubin concentration < 57 micromol/l six weeks after the operation. Thus, children with bilirubin concentrations above this level should be carefully and frequently monitored with regard to a transplantation requirement in order to optimize pretransplant management.     

Long-term results of biliary atresia in the era of liver transplantation

Purpose

The purpose of this study was to analyze the survival of patients with biliary atresia (BA) after Kasai operation and liver transplantation (LT) and to analyze the factors affecting survival.

Methods

Seventy-two patients diagnosed with BA were operated on between April 1995 and December 2009 and retrospectively analyzed.

Results

Out of the 72 patients, 59 received Kasai operation and 13 received LT without prior Kasai operation. Twenty-seven patients received LT after Kasai operation. Survival with native liver was 39 % at 10 years. With the application of LT, overall 10-year survival for patients with BA was 94.9 %. Among patients alive with native livers after Kasai operation, 14 patients (58.3 %) have at least one complication associated with biliary cirrhosis and portal hypertension. Age at which Kasai operation was performed (60 days) and postoperative normalization of bilirubin were independent risk factors for survival with the native liver, according to multivariate analysis (HR 2.90, p = 0.033 and HR 9.89, p = 0.002).

Conclusions

Survival of BA patients has greatly increased in the era of LT. However, many patients surviving with native livers after Kasai operation continue to have signs of biliary cirrhosis and abnormal liver function.     

胆道闭锁Kasai术后肝脏纤维化及生化指标变化趋势的横断面研究

目的 研究胆道闭锁患儿Kasai术后肝脏纤维化及生化指标的变化趋势.方法 采用横断面研究方法,对2013年1月至2013年12月于首都医科大学附属北京儿童医院普外科随访的胆道闭锁Kasai术后患儿进行复查资料收集,术后随访时间6个月以上,资料完整的121例纳入研究.按照Kasai术后胆红素降至正常的时间,以术后3个月、6个月为界分为优、良、差三组,获取患儿术时年龄、术前和术后Fibroscan肝脏硬度测量值及生化结果,绘制趋势图并进行统计学分析研究各组患儿Kasai术后肝脏纤维化及生化指标的变化趋势.结果 纳入本研究胆道闭锁患儿共121例,男69例(57.0％),女52例(43.0％);其中优组63例(52.1％),良组34例(28.1％),差组24例(19.8％).三组患儿术时年龄差异无统计学意义.三组患儿Fibroscan肝脏硬度测量值在术后1年内波动进展,1年后趋于稳定;单因素方差分析及秩和检验结果显示优良组差异无统计学意义,优良组与差组患儿Fibroscan肝脏硬度测量值在术后1年内差异均有统计学意义.优良组患儿总胆红素在术后前3个月下降较快,随后缓慢下降,至术后6个月稳定于正常值,而差组患儿总胆红素术后前2个月下降较快,但随后出现较大波动.三组患儿ALT趋势图均在术后1个月出现波峰,优良组术后1～6个月有所下降,但之后持续波动不能稳定,差组持续波动;三组患儿AST术后6个月内有所下降,但之后波动较大不能稳定.三组患儿CGT术后1个月达到最高峰,至术后6个月下降较快,随后逐渐趋于稳定小幅波动.结论 ①胆道闭锁患儿Kasai术后1年内肝脏纤维化波动性进展,自肝存活超过1年者肝纤维化情况进展缓慢趋于稳定,优组患儿在2年后更加稳定;②Kasai术后1个月内胆红素下降最快,3～6个月胆红素可降至正常的患儿,其胆红素水平可维持长期正常;③肝脏炎症、胆管反应、功能损害在术后仍继续进展,术后1个月开始减轻,术后6个月趋于稳定.     

Enzymatic studies and isoenzyme pattern of gammaglutamyl transpeptidase (GGTP) in Indian childhood cirrhosis (CC)

Histopathological studies of liver cell showing necrosis, parenchymal cell injury and microsomal cell damage are known to affect membrane bound enzymes such as gamma-glutamyl transpeptidase (GGTP), alkaline phosphatase (AP) and 5′-nucleotidase (5′-NT). The significant rise in GGTP, AP and 5′-NT indicates the damage of microsomes of parenchymal cell in Indian Childhood Cirrhosis (ICC) patients. SGPT/AP ratio may be an index for distinguishing ICC with other liver diseases. The isoenzyme pattern of GGTP in sera of control and ICC subjects have one band prominent activity. Similarly biopsy samples of control and ICC subjects show one prominent band of GGTP activity. The appearance of isoenzyme of GGTP in blood circulation is an index of microsome damage, cell necrosis and parenchymal cell injury. The isoenzyme pattern of GGTP could be a diagnostic test for ICC.     

Evaluation of a standardized protocol in the use of steroids after Kasai operation

Although the Kasai operation is still the treatment of choice for infants with biliary atresia, the long-term success rate, as defined by survival without transplantation, is only about 25-40%. It has been proposed that post-operative inflammatory changes affect the bile flow and eventually lead to cholangitis and liver failure. Recent case reports have suggested that the administration of steroids post-operatively can improve outcomes. Since 2004, our unit has adopted a strict protocol for the use of post-operative steroids for patients who undergo Kasai operation. The aim of this study is to access the early outcomes of these patients. A retrospective analysis was carried out for all patients who received Kasai operation between 1996 and 2006. For the treatment group, patients all received prednisolone at 4 mg/kg 1 week after operation as guided by protocol. The demographics and outcomes, including post operative bilirubin level, episodes of cholangitic attack, the need for early liver transplantation (transplant within 1 year of Kasai), and transplantation-free survival, were noted. Statistical analysis was done using Fisher's exact test and unpaired t-test when appropriate. A value of P < 0.05 was considered to be statistically significant. Kasai operation was performed in 30 patients (11 boys and 19 girls) during the study period. Thirteen patients received post-operative prednisolone according to protocol. The average age at operation and the mean preoperative bilirubin levels for the steroid and non-steroid group were not significantly different. A normal post-operative bilirubin (defined as bilirubin level less than 20 mumol/L) was achieved at 6 months in 7 (53.9%) patients who received steroid and 8 (47.0%) patients who did not (P = 0.71). A statistically significant reduction in the post-operative bilirubin level was also seen at 3 and 6 months in the steroid group. Early liver transplantation was required in 5 (38.5%) patients with steroid and 5 (29.4%) patients without it (P = 0.60). No significant difference in terms of cholangitic attack was observed. There was also no steroid-associated complication reported. We conclude that lower post-operative bilirubin level can be achieved with the routine use of prednisolone. However, there is no statistical improvement in terms of early liver transplantation and cholangitis. This may be attributed to the small sample size of our study population. Based on this pilot study, a multi-centre randomized trial is needed.     

Different polyunsaturated fatty acid profiles in patients with biliary atresia after successful Kasai operation and liver transplantation

Background  Although Kasai operation eliminates jaundice in patients with biliary atresia, inflammation at Glisson’s area persists and fibrosis advances slowly to liver cirrhosis. Profiles of polyunsaturated fatty acids, on which metabolic products have an immunoregulative effect, were investigated in this study. Methods  Blood samples were obtained from patients including 21 jaundice-free patients with biliary atresia after Kasai operation (native liver group) and 18 patients in whom Kasai operation failed and liver transplantation was performed (transplantation group). All of these patients are without any complications for more than 6 months. Blood samples from 18 patients with inguinal hernia were assigned as normal controls (control group). Profiles of fatty acids in whole serum lipids were measured using gas chromatography. The n-3/n-6 ratio of polyunsaturated fatty acids was compared among the three groups. Results  The n-3/n-6 ratio was 0.114 in the native liver group, which was significantly lower than 0.145 in the transplantation group (P = 0.009) and 0.158 in the control group (P = 0.004). There was no significant difference between the transplantation and control groups (P = 0.83). Results  The n-3/n-6 ratio was abnormal after Kasai operation despite normal liver function. This seems to be one factor of persisting inflammation in Glisson’s area.     

Reappraise the effect of redo-Kasai for recurrent jaundice following Kasai operation for biliary atresia in the era of liver transplantation

Purpose

This study was conducted to reappraise the efficacy of redo-Kasai (or revision) in the era of liver transplantation as a treatment option in those patients with recurrent jaundice after initially successful Kasai procedure.

Methods

We studied ten patients that received redo-Kasai, among a total of 102 patients diagnosed with biliary atresia after receiving Kasai operation from 1986 to 2011.

Results

Kasai operation was done at a median age of 55?days and redo-Kasai at 150?days. The bilirubin levels returned to normal in six patients after the procedure. Four of six enjoyed jaundice-free survival with native liver till the time of last follow-up. Three patients died and three received liver transplantation (LT). Only one out of seven patients with three or more episodes of cholangitis survived with native liver, while all the three patients with 1 or 0 episode survived with native liver. The difference was significant (P?=?0.033). Re-do Kasai did not result in more blood loss or operative time during LT.

Conclusion

Redo-Kasai is still valuable in the era of LT and the episodes of cholangitis are the decisive factors affecting the outcome of the procedure.     

Pre-operative time course changes in liver function tests in biliary atresia: Its usefulness in the discrimination of biliary atresia in early infancy

In order to investigate the possibility of early discrimination of extrahepatic biliary atresia from other cholestatic diseases, a series of results of liver function tests in infants with cholestatic diseases were reviewed. The results of routine liver function tests (LFT) recorded in patients' charts were reviewed within 12 weeks after birth in 47 infants with extrahepatic biliary atresia (BA), 10 infants with neonatal hepatitis (NH) and 130 age-matched control infants (CO) without cholestatic diseases. The mean of each test value for each week after birth was derived from the actual data examined in each infant. No differences were observed between BA and CO in the levels of aminotransferases within 2 weeks after birth. Total bilirubin and direct bilirubin levels were significantly different between BA and CO within 1 week after birth (16.1 ± 3.2 mg/dL vs 11.1 ± 4.5 mg/dL, 4.6 ± 2.6 mg/dL vs 0.7 ± 0.3 mg/dL, respectively) The direct bilirubin-total bilirubin ratio exceeded 25% within the first week in BA. The individual values of direct bilirubin (DB) exceeded 2 mg/dL within the first week in all infants with BA, while none of the individual values exceeded 1.6 mg/dL in CO. Gamma-glutamyl transpeptidase levels were significantly different between BA and CO at 4 weeks (432 ± 272 IU/L vs 79 ± 43 IU/L) and thereafter; and were significantly different between BA and NH at 6 weeks (314 ± 232 IU/l vs 69 ± 58 IU/L) and thereafter. These data suggest that the determination of direct bilirubin within 1 week after birth can detect extrahepatic biliary atresia patients from those with physiologic jaundice, and γ-glutamyl transpeptidase levels may discriminate BA from NH at no later than 6 weeks of age.     

胆道闭锁患儿Kasai术后早期胆管炎相关危险因素分析

目的 探讨影响胆道闭锁患儿(biliary atresia,BA)经典Kasai术后早期胆管炎发生的相关因素.方法 对本组中35例BA患儿的临床资料应用二项分类logistic同归分析方法作回顾性分析.结果 胆道闭锁患儿术后近期胆管炎发生与术后胆汁引流效果、术后辅以激素治疗及术中预留胆支长度有显著相关性,而与患儿性别、手术日龄、术前总胆红素及肝功能、手术前后辅以熊去氧胆酸和苯巴比妥利胆退黄治疗、术中设置防反流瓣及术后抗感染力度等因素无关.结论 胆道闭锁患儿Kasai术后胆汁引流效果好,辅以激素治疗,同时术中预留胆支长度充分的BA患儿,其术后不易发生早期胆管炎;反之,患儿发生早期胆管炎风险增加.

Abstract：

Objective To evaluate the factors affecting the early post-operative cholangeitis after classical Kasai operation for biliary atresia (BA) in children. Methods The clinical data of thirty-five BA children from pediatric surgery department of Nanjing Childrens Hospital was retrospectively analyzed using binary logistic regression analysis. Results The occurrence of early cholangitis after classical Kasai operation was found to correlate with post-op biliary drainage effect, hormone therapy and the length of Roux-loop in operation. No correlation could be established between early cholangeitis and sex,age, total bilirubin and pre-op liver function, ursodeoxycholic and luminal therapy, the installation of anti-refluxing valve in operation and the dosage of antibiotics. Conclusions Good biliary drainage,hormone therapy and sufficient length of Roux-loop were associated with decreased risk of early cholangitis.     

2021年第39卷第1期目次页

目的分析婴儿期胆汁淤积性和非胆汁淤积性肝病的临床特点。方法回顾分析肝病婴儿的临床资料,比较胆汁淤积和非胆汁淤积肝病婴儿的临床差异。结果1985例肝病婴儿中,男性866例、女性1119例,入院月龄为(2.88±3.08)月。胆汁淤积症婴儿477例(24.0%),非胆汁淤积症婴儿1508例(76.0%)。单因素分析示,胆汁淤积婴儿的月龄小于非胆汁淤积婴儿,总胆红素、直接胆红素、γ-谷氨酰转肽酶、碱性磷酸酶、总胆汁酸水平高于非胆汁淤积婴儿,差异均有统计学意义(P<0.05)。多元logistic回归分析示,γ-谷氨酰转肽酶、碱性磷酸酶和总胆汁酸水平越高,月龄、白蛋白水平越低,发生胆汁淤积的可能性越高。结论在婴儿期,相比非胆汁淤积性肝病,胆汁淤积性肝病起病早,γ-谷氨酰转肽酶、碱性磷酸酶和总胆汁酸水平高。     

Does breast feeding influence liver biochemistry?

OBJECTIVE: It is assumed that early feeding can affect liver biochemistry because breast-fed infants have a higher risk of hyperbilirubinemia than formula-fed infants. The authors sought to determine how feeding mode affected liver biochemistry in healthy term infants. METHODS: Healthy term infants were followed up during infancy with a monthly questionnaire about feeding mode. Blood samples were obtained at 2, 6, and 9 months. Liver biochemistry (serum albumin, alkaline phosphatase, lactic dehydrogenase, aspartate aminotransferase [AST], and bilirubin), total insulin-like growth factor 1 (IGF-I), and insulin growth factor binding protein 3 (IGFBP-3) were determined at all ages. RESULTS: Mean AST and bilirubin were significantly higher in breast-fed infants at 2 and 6 months. In addition, mean albumin levels were higher in breast-fed infants at 2 months. Alkaline phosphatase, IGF-I, IGFBP-3, and lactic dehydrogenase levels did not differ between the feeding groups. AST levels did not correlate significantly with bilirubin, albumin, alkaline phosphatase, or lactic dehydrogenase values. There was a strong positive association between AST and IGF-I at 2 months (r = 0.47, P = 0.004). CONCLUSION: Cytomegalovirus infection, vitamin K deficiency, and macromolecular forms of AST could be an explanation for a higher AST level among breast-fed infants. However, no other clinical or paraclinical sign of liver disease was seen, all infants were given oral vitamin K, and the AST did not rise to levels comparable to those seen in individuals with macromolecular AST. The authors speculate the most likely explanation of the elevated AST is induction of hepatocytes by factors in human milk. This is supported by the higher albumin levels in breast-fed infants and the positive association between AST and IGF-I.